KIAA0702
NCKX1
SLC24A1
UniProt:O60721 SLC24A1
MSK1
RPS6KA5
UniProt:O75582 RPS6KA5
DHRS3
UniProt:O75911 DHRS3
LRAT
UniProt:O95237 LRAT
MADHIP
SARA
SMADIP
UniProt:O95405-1 ZFYVE9
ZFYVE9
DNAL4
UniProt:O96015 DNAL4
LDLR
UniProt:P01130 LDLR
CDC2
CDC28A
CDK1
CDKN1
P34CDC2
UniProt:P06493 CDK1
MMP3
STMY1
UniProt:P08254 MMP3
FUR
FURIN
PACE
PCSK3
UniProt:P09958 FURIN
RBP3
UniProt:P10745 RBP3
SRC
SRC1
UniProt:P12931-1 SRC
PKCA
PRKACA
PRKCA
UniProt:P17252 PRKCA
PTP1B
PTPN1
UniProt:P18031 PTPN1
PLC1
PLCG1
UniProt:P19174 PLCG1
RPS6KB1
STK14A
UniProt:P23443 RPS6KB1
ERK1
MAPK3
PRKM3
UniProt:P27361 MAPK3
ERK2
MAPK1
PRKM1
PRKM2
UniProt:P28482 MAPK1
ADORA2
ADORA2A
UniProt:P29274 ADORA2A
PPM1A
PPPM1A
UniProt:P35813 PPM1A
ADCYAP1R1
UniProt:P41586 ADCYAP1R1
JNK1
MAPK8
PRKM8
SAPK1
SAPK1C
UniProt:P45983 MAPK8
MAPKAPK2
UniProt:P49137 MAPKAPK2
ABCA4
ABCR
UniProt:P78363 ABCA4
CDK5
CDKN5
UniProt:Q00535 CDK5
PTP2C
PTPN11
SHPTP2
UniProt:Q06124 PTPN11
BAMBI
NMA
UniProt:Q13145 BAMBI
MAP2K5
MEK5
MKK5
PRKMK5
UniProt:Q13163 MAP2K5
BMK1
ERK5
MAPK7
PRKM7
UniProt:Q13164 MAPK7
PDE3B
UniProt:Q13370 PDE3B
ORCA
OSIL
SQSTM1
UniProt:Q13501 SQSTM1
GRK1
RHOK
UniProt:Q15835 GRK1
RPE65
UniProt:Q16518 RPE65
PLB
PLB1
UniProt:Q6P1J6 PLB1
C3orf9
CLP46
KTELC1
MDS010
MDSRP
POGLUT1
UniProt:Q8NBL1 POGLUT1
ARSDR1
CGI-82
PSDR1
RDH11
UniProt:Q8TC12 RDH11
RDH1
RDH5
UniProt:Q92781 RDH5
ARHGEF1
UniProt:Q92888 ARHGEF1
CUL5
UniProt:Q93034 CUL5
VACM1
RDH12
UniProt:Q96NR8 RDH12
MGLL
UniProt:Q99685 MGLL
MKNK1
MNK1
UniProt:Q9BUB5 MKNK1
MG61
PORC
PORCN
PPN
UniProt:Q9H237 PORCN
FUT12
KIAA0180
POFUT1
UniProt:Q9H488 POFUT1
FLRF
NRDP1
RNF41
SBBI03
UniProt:Q9H4P4 RNF41
PRRDH
RDH8
UniProt:Q9NYR8 RDH8
CHIP
PP1131
STUB1
UniProt:Q9UNE7 STUB1
Active PLCG1 hydrolyses PIP2
DAG stimulates protein kinase C-delta
p-RAF binds 14-3-3 beta/alpha
Transient dissociation of 14-3-3 upon Ras binding
Stabilisation of RAS:RAF by 14-3-3
Stabilisation of RAF by further phosphorylation
Phosphorylated human RAF1 binds to RAS:GTP complex
Activated RAF1 complex binds MEK
RAF1 phosphorylates MEK1
RAF1 phosphorylates MEK2
Adenylate cyclase produces cAMP
cAMP induces dissociation of inactive PKA tetramers
PKA catalytic subunit translocates to the nucleus
PKA phosphorylates CREB
Dimerisation of CREB
Calmodulin binds CaMK IV
CamKIV enters the nucleus
CaMK IV autophosphorylation
CaMK IV phosphorylates CREB
Calmodulin activates Cam-PDE 1
cAMP hydrolysis by Cam-PDE 1
Inhibition of GRK2 by calmodulin
PKC phosphorylates GRK2
JAK2 phosphorylation
PRLR associates with JAK2
PRLR:JAK2 dimerizes
Prolactin receptor ligands bind the prolactin receptor
PRLR activation
SH2B binds JAK2
Tyrosine phosphorylation of PRLR
PRLR binds STAT5
PRLR-bound STAT5 is phosphorylated
PRLR binds SHP2 (PTPN11)
SHP2 is phosphorylated
PRLR is phosphorylated at Ser-349
PRLR binds SCF beta-TrCP complex
Prolactin receptor is internalized
Complex of NOTCH1 with its ligand is cleaved to produce NEXT1
NOTCH2-ligand complex is cleaved to produce NEXT2
Notch 3-ligand complex is cleaved to produce NEXT3
Notch 4-ligand complex is cleaved to produce NEXT4
ABCA4 mediates atRAL transport
atRAL(membrane) is transported to atRAL(cytosol) by ABCA4
Vasopressin receptor type 2 bind vasopressin
G alpha (s) activates adenylate cyclase
Integrin alpha5beta1 binds fibronectin
Transport of Ca++ from platelet dense tubular system to cytoplasm
Integrin alpha2beta1 collagen adhesion
TP receptor can bind thromboxane
PIP3 recruits PDK1 and AKT to the membrane
Translocation of RIAM to plasma membrane
Activation of Talin
Integrin alphaIIb beta3 activation
Interaction of integrin alphaIIb beta3 with Fibrinogen
Clustering of Integrin alphaIIb beta3 complexes
Release of CSK from SRC
Dephosphorylation of inactive SRC by PTPB1
Autophosphorylation of SRC
Translocation of FADK1 to Focal complexes
Autophosphorylation of FADK1 at Y397
Phosphorylation of pFADK1 by SRC
Recruitment of GRB2 to p-FADK1
Interaction of SOS with GRB2 bound to FADK1
Recruitment of p130Cas to FADK1
Phosphorylation of p130Cas by SRC-FADK1 complex
Crk binding to p130cas
Integrin alpha IIb beta3 T779 phosphorylation blocks SHC binding
Activated integrin alphaIIb beta3 binds SHC1
SHC1 bound to integrin alphaIIb beta3 is phosphorylated somehow
SHC1 dissociates from integrin alphaIIb beta3
SYK binds to integrin alphaIIb beta3
SYK activation by SRC
Alpha-2 adrenoceptors bind catecholamines
Binding of IP3 to IP3 receptor
Calcium and Diacylglycerol activate CalDAG-GEFs (RasGRPs)
Activation of Protein Kinase C novel isoforms
DAG activation of TRPC channels
DAG is metabolized by DAGL to 2-AG
2-AG hydrolysis to arachidonate by MAGL
DAG kinase produces phosphatidic acid from DAG
Calcium binds calmodulin
MAC1 binds JAM-C
VLA-4 binds JAM-B
LFA1 binds JAM-A
Integrin alphaXbeta2 binds JAM-C
Interaction of integrin alphaVbeta3 with PECAM-1
Basigin binds to integrins
Phosphorylation of PDE3B
Hydrolysis of cAMP to 5' AMP by Phosphorylated PDE3B
Pro-EGF is cleaved to form mature EGF
EGFR binds EGF ligand
EGFR dimerization
EGFR autophosphorylation
Phosphorylation of EGFR by SRC kinase
Phospholipase C-gamma1 binds to the activated EGF receptor
EGFR activates PLC-gamma1 by phosphorylation
Active PLC-gamma1 dissociates from EGFR
GRB2 binds SOS1
GRB2:SOS1 complex binds to EGF:EGFR complex
SOS1-mediated nucleotide exchange of RAS (EGF:EGFR:GRB2:SOS1)
SHC1 binds to the phosphorylated EGF receptor:ligand complex
SHC1 phosphorylation by phosphorylated EGFR
GRB2:SOS1 binds to phosphorylated SHC1 in complex with EGFR
SOS1-mediated nucleotide exchange of RAS (EGF:EGFR:SHC1:GRB2:SOS1)
Binding of GRB2 to GAB1
Binding of PIK3 regulatory alpha subunit to GRB2:GAB1
GRB2:GAB1:PIK3R1 binds to phosphorylated EGFR
PIK3 catalytic subunit binds to EGF:EGFR:GRB2:GAB1:PIK3R1
PIK3 converts phosphatidylinositol-4,5-bisphosphate (PIP2) to phosphatidylinositol-3,4,5-trisphosphate (PIP3)
Gab1 binds phosphatidylinositol-3,4,5-trisphosphate
Gab1:Grb2 binds to EGF:Phospho-EGFR
Gab1 phosphorylation by EGFR kinase
Activation of SHP2 through the binding to phospho-Gab1
Dephosphorylation of Gab1 by SHP2
SHP2 dephosphorylates Tyr 992 on EGFR
Dephosphorylation of PAG by SHP2
Sustained activation of SRC kinase by SHP2
Binding of CBL to EGFR
Phosphorylation of CBL (EGFR:CBL)
CBL binds and ubiquitinates phosphorylated Sprouty
Ubiquitination of stimulated EGFR (CBL)
CBL binds to GRB2
Localization of CBL:GRB2 to the membrane
Phosphorylation of CBL (EGFR:GRB2:CBL)
Ubiquitination of stimulated EGFR (CBL:GRB2)
Sprouty lures cytosolic CBL away from EGFR
Sprouty lures membrane-bound CBL away from EGFR
CDC42 lures CBL away from the receptor
Beta-Pix pushes CIN85 away from CBL
CBL escapes CDC42-mediated inhibition by down-regulating the adaptor molecule Beta-Pix
Assembly of EGFR complex in clathrin-coated vesicles
Assembly in clathrin-coated vesicles (CCVs)
EGFR non-clathrin mediated endocytosis
CBL ubiquitinates Sprouty
CBL-mediated ubiquitination of CIN85
Sprouty sequesters CBL away from active EGFR
FGFR1b binds to FGF
Autocatalytic phosphorylation of FGFR1b
FGFR1c binds to FGF
Autocatalytic phosphorylation of FGFR1c
FGFR2b binds to FGF
Autocatalytic phosphorylation of FGFR2b
FGFR2c binds to FGF
Autocatalytic phosphorylation of FGFR2c
FGFR3b binds to FGF
Autocatalytic phosphorylation of FGFR3b
FGFR3c binds to FGF
Autocatalytic phosphorylation of FGFR3c
FGFR4 binds to FGF
Autocatalytic phosphorylation of FGFR4
FGFR4 binds BetaKlotho-bound FGF19
Autocatalytic phosphorylation of BetaKlotho-bound FGFR4
FGFR1c binds to Klotho-bound FGF23
Autocatalytic phosphorylation of Klotho-bound FGFR1c
Activated FGFR binds FRS2alpha
Activated FGFR binds FRS2beta
Phosphorylation of FRS2-alpha by activated FGFR
Phosphorylation of FRS2-beta by activated FGFR
Activated FGFR and FRS2 bind to SHP2
Activated FGFR-alpha:p-FRS2 bind to SHP2
SHP2 is phosphorylated by activated FGFR
GRB2:SOS1 binds to p-FRS2:activated FGFR
Ras nucleotide exchange by GRB2:SOS1 bound to p-FRS2:activated FGFR
Activated FGFR binds PLC-gamma
PLC-gamma phosphorylation by FGFR
Activated PLC gamma release by activated FGFR
Activated FGFR recruits SHC1
SHC1 is phosphorylated
GRB2:SOS1 is recruited to activated FGFR through p-SHC1
Ras nucleotide exchange by GRB2:SOS1 through p-SHC
GRB2:GAB1:PI3Kreg binds directly to p-FRS2:activated FGFR
GRB2:GAB1:PI3Kreg binds to p-SHP2 on p-FRS2:activated FGFR
PI3K catalytic subunit is recruited by FGFR-associated PI3KR1
PI3K catalytic subunit binds to GRB2:GAB1:PI3Kreg (indirect)
FGFR-associated PI3K phosphorylates PIP2 to PIP3
FGFR associated PI3K phosphorylates PIP2 to PIP3
Activated ERK1/2 threonine-phosphorylate FRS2alpha.
p-CBL:GRB2 binds p-FRS2alpha:activated FGFR
CBL ubiquitinates FRS2 and FGFR
PPA2A dephosphorylates SPRY2
SPRY2 translocates to the plasma membrane
SRC phosphorylates SPRY2 on Y55 and Y227
SPRY2 binds GRB2
SPRY2 binds CBL
Phosphorylated SPRY2 is ubiquitinated by CBL
CBL dissociates from ubiquitinated p-SPRY2
SPRY2 is phosphorylated by phosphorylated MNK1
SPRY2 is serine phosphorylated in response to MAPK activation
B-RAF dissociates from S111/S120 p-SPRY2
SHP2 dephosphorylates SPRY2
p-MEK phosphorylates ERK
Dissociation of p-ERK from p-MEK
p-ERK dimerizes
Digestion of retinyl palmitate by extracellular PTL:colipase
PNLIP:CLPS hydrolyses RPALM to atROL and PALM
Cleavage of retinyl palmitate by PLB1
PLB1 hydrolyses RPALM to atROL
Membrane retinol binds to cytosolic RBP2
atROL binds to RBP2
BCMO1:Fe2+ oxidises betaC to atRAL
Oxidation of beta-carotene to all-trans-retinal
atRAL binds to RBP2
RDH11 reduces RBP2:atRAL to RBP2:atROL
AKRs reduce RBP2:atRAL to RBP2:atROL
LRAT esterifies RBP2:atROL and FACYLs to atREs
atREs binds to nascent CM
Chylomicron secretion into the lymphatic system
Cytosolic CMs translocate to extracellular region
Nascent CMs transform into mature CMs
LPL hydrolyses TGs from mature CMs
Lipoprotein lipase (LPL) hydrolyses triacylglycerols (TGs) from mature chylomicrons (CM)
Circulating chylomicron remnants can be directly cleared by the LDL receptor
LDLR transports extracellular CR:atREs to cytosol
CR remnants bind to apoE, enhanced by HSPG, in preparation for internalisation
CR:atREs binds apoE and HSPG
LRPs transport extracellular CR:atREs:HSPG:apoE to cytosol
Remnant CMs bound to apoE and HSPG are cleared by LDL receptor-related proteins
NREH hydrolyses atREs to atROL and FAs
Retinyl esters are hydrolysed to retinol in hepatocytes
NREH hydrolyses atREs (HSPG:apoE) to atROL and FAs
Retinyl esters (complexed with HSPG:apoE) are hydrolysed to retinol in hepatocytes
atROL binds RBP1 (parenchymal cell)
Parenchymal atROL translocates to HSCs
atROL delivered to stellate cells for storage
atROL binds RBP1
LRAT esterifies RBP1:atROL and FACYLs to atREs
A REH hydrolses atREs to atROL and FAs
HSC cytosolic atROL translocates to extracellular region
atROL secreted into bloodstream
RBP4 binds atROL
RBP4:atROL binds TTR
TTR:RBP:atROL binds to STRA6 receptor
All-trans-retinol is taken up by cells expressing STRA6 receptor
atROL (extracellular) is transported to cytosol by STRA6
Before esterification, retinol binds to RBP1 in RPE
atROL binds RBP1 to form RBP1:atROL
LRAT esterifies all-trans-retinol in RPE
RPE65 isomero-hydrolyses atREs to 11cROL
Retinoid isomerohydrolase isomero-hydrolyses retinyl esters to 11-cis-retinol
RDHs oxidise 11-cis-retinol to 11-cis-retinal
RDHs oxidise 11cROL to 11cRAL
RDH5 oxidises 11-cis-retinol to 11-cis-retinal
RDH5 oxidises 11cROL to 11cRAL
11cRAL (RPE) translocates to photoreceptor outer segment
11-cis-retinal binds to rhodopsin
11cRAL binds to opsin to form RHO:11cRAL
Photons induce isomerization of 11cRAL to atRAL
Rhodopsin activation
NRPE is a substrate for ABCA4
NRPE dissociates to atRAL and PE
atRAL diffuses through membranes to cytosol
atRAL(membrane) diffuses to atRAL(cytosol)
RDH12 reduces atRAL to atROL
RDH8 reduces atRAL to atROL
RBP3 regulates the transport of atROL from ROS to RPE
RBP3 regulates atROL taken up by Muller cells
An atROL isomerase isomerises atROL to 11cROL
A REH hydrolyses 11cRE to 11cROL
11cROL translocates from Muller cells to cone photoreceptor cells
11cROL binds to RLBP1 to form RLBP1:11cROL
RLBP1 binds atROL
11cRDH oxidises 11cROL to 11cRAL
Photons induce isomerisation of 11cRAL to atRAL
atRAL is hydrolysed from R*
atRAL is reduced to atROL
MII catalyses GDP/GTP exchange on Gt
Gt-GTP dissociates to GNAT1-GTP and GNB1:GNGT1
GNAT1-GTP binds PDE6 and activates it
PDE hydrolyses cGMP to GMP
cGMP:CNG transports Na+ and Ca2+ into the rod outer segment
NCKX1 exchanges Na+ for Ca2+/K+
NCKX1 removes Ca2+ from the rod outer segment
Decreased cGMP closes cation channels
cGMP dissociates from CNG channels
METAP1/2 demethylates GNAT1
NMT1/2 transfer MYS to GNAT1
FNTA:FNTB transfers FARN to GNGT1
Farnesyltransferase complex farnesylates the gamma subunit of transducin
Phosphorylated SMAD2 and SMAD3 form a complex with SMAD4
Unknown N-acyltransferase N-acylates glycine residue in GNAT1
Unknown NAT N-acylates Gly in GNAT1
GRK1 phosphorylates MII to p-MII
GRK1 phosphorylates MII to p-S334,S338,S343-MII
Ca2+ and recoverin restrict GRK1 activity
RCVRN:Ca2+ binds to and inhibits GRK1
SAG binds p-MII to form p-MII:SAG
atRAL dissociates from p-MII:SAG
p-MII:SAG dissociates to p-RHO and SAG
PP2A dephosphorylates p-RHO to RHO
GNAT1-GTP hydrolyses its bound GTP to GDP
PRKCA/Q phosphorylate RGS9-1:GN5B:RGS9BP
PRKCA/Q phosphorylate RGS9-1:GN5B:RGS9BP to form p-S478-RGS9-1:GN5B:RGS9BP
GNAT1-GDP binds to GNB1:GNGT1
The SMAD2/3:SMAD4 complex transfers to the nucleus
GUCA binds Ca2+ to form GUCA:Ca2+
GUCYs converts GTP to cGMP
cGMP synthesis by guanylyl cyclase
cGMP binds CNG channel to form cGMP:CNG channel
CALM1:Ca2+ binds CNG channel
Calmodulin:Ca2+ lowers CNG channel sensitivity to cGMP
Phosphorylation of SMAD2 and SMAD3 linker regions by CDK8 or CDK9
WWTR1 binds SMAD2/3:SMAD4 heterotrimer
WWTR1:SMAD translocates to the nucleus
NOTCH1 binds DLL1
NOTCH1 binds DLL4
NOTCH1 binds JAG1
NOTCH1 binds JAG2
Ubiquitination of DLL/JAG ligands upon binding to NOTCH1
NEXT1 is cleaved to produce NICD1
NICD1 traffics to nucleus
DTX binds NOTCH1
Contactin-1 (CNTN1) binds NOTCH1
Cleavage of CNTN1:NOTCH1 complex releases NICD1
WWTR1:SMAD stimulates transcription of SMAD7
NOTCH1 binds DNER
Cleavage of DNER:NOTCH1 complex releases NICD1
DTX recruits beta-arrestin (ARRB) to NOTCH
ARRB mediates NOTCH1 ubiquitination
ITCH binds DTX
ITCH ubiquitinates DTX
NOTCH1 binds DLL/JAG ligand in cis
NOTCH1 binds DLK1
NOTCH1 associates with negative regulators NUMB and ITCH
Ubiquitination of NOTCH1 by ITCH in the absence of ligand
WWTR1:SMAD stimulates transcription of SERPINE1 while TGIF:SMAD and SMAD7 inhibit it
NICD1 displaces co-repressor complex from RBPJ (CSL)
NICD1 in complex with RBPJ (CSL) recruits MAML
HES1 binds TLE
MAML in complex with NICD1 recruits CDK8
NICD1 is phosphorylated by CDK8
Phosphorylated NICD1 binds FBXW7
Ubiquitination of NICD1 by FBWX7
NICD1 binds HIF1A
RNF111 binds SMAD7
RNF111 ubiquitinates SMAD7
SMAD2/3:SMAD4 heterotrimer forms a complex with RBL1, E2F4/5 and DP1/2
NEXT2 is cleaved to produce NICD2
NEXT3 is cleaved to produce NICD3
NEXT4 is cleaved to produce NICD4
MYC trancscription is negatively regulated by SMAD2/3:SMAD4:RBL1:E2F4/5:DP1/2 complex
SMAD2/3:SMAD4 heterotrimer binds SP1
SMAD2/3:SMAD4:SP1 complex stimulates transcription of CDKN2B
MEN1 binds SMAD2/3:SMAD4 heterotrimer
SMAD2/3:SMAD4 complex positively regulates JUNB transcription
SKI/SKIL binds SMAD complex, suppressing TGF-beta signaling
SMAD2/3 activation induces binding of RNF111/SMURF2 to SKI/SKIL
Ubiquitination of SKI/SKIL by RNF111/SMURF2
TRIM33 (Ectodermin) binds SMAD heterotrimer in the nucleus
TRIM33 monoubiquitinates SMAD4
Ubiquitinated SMAD4 translocates from the nucleus to the cytosol
USP9X (FAM) binds to ubiquitinated SMAD4
USP9X (FAM) deubiquitinates SMAD4
NEDD4L binds phosphorylated linker region of SMAD2/3
NEDD4L ubiquitinates SMAD2/3
SMURF2 binds SMAD3 phosphorylated in the linker region
SMURF2 monoubiquitinates SMAD3
TGIF recruits HDAC1 to SMAD2/3:SMAD4 heterotrimer
PARP1 binds SMAD2/3:SMAD4 heterotrimer
PARP1 ADP-ribosylates SMAD3 and SMAD4
PPM1A protein phosphatase binds phosphorylated SMAD2/3
PPM1A dephosphorylates nuclear SMAD2/3
Dephosphorylated SMAD2/3 translocates to the cytosol
GABAB heterodimeric receptor binds GABA
G alpha (i) inhibits adenylate cyclase
G alpha-olf:GTP binds to Gi alpha1:GTP:adenylate cyclase complex
Adenylate cyclase increases the GTPase activity of G alpha-olf
Adenylate cyclase increases the GTPase activity of Gi alpha
Dissociation of the Gi alpha:G olf complex
NICD2 traffics to the nucleus
NICD3 traffics to the nucleus
NICD4 traffics to the nucleus
Insulin binding
Autophosphorylation of insulin receptor
Binding of SHC to insulin receptor
Phosphorylation of SHC
Dissociation of SHC-P from insulin receptor
GRB2:SOS binds to SHC-P
SOS mediated nucleotide exchange of RAS (SHC)
Binding of IRS to insulin receptor
Phosphorylation of IRS
Dissociation of IRS-P from insulin receptor
PI3K activation
PIP2 conversion to PIP3
Phosphorylation of TSC2 by PKB
Phosphorylation of complexed TSC2 by PKB
GTP loading by Rheb
Formation of active mTORC1 complex
Activation of S6K1
Phosphorylation of Ribosomal protein S6 by activated S6K1
Phosphorylation and inactivation of eEF2K by activated S6K1
Phosphorylation and activation of eIF4G by activated S6K1
Phosphorylation and activation of eIF4B by activated S6K1
Phosphorylation of 4E-BP1 by activated mTORC1
Dissociation of phosphorylated 4EBP1 from eIF4E
LKB1 forms a trimeric complex with STRAD and MO25
Activation of cytosolic AMPK by phosphorylation
AMPK is dephosphorylated
Phosphorylated AMPK binds AMP
AMPK phosphorylates Raptor
p-AMPK phosphorylates TSC2
TSC2 activates intrinsic GTPase activity of Rheb
PDK1 attachment to plasma membrane
PKB attachment to plasma membrane
Phosphorylation of AKT2 by PDK1
GRB2:SOS binds IRS-P
SOS mediated nucleotide exchange of RAS (IRS)
De-phosphorylation of IRS
De-phosphorylation of SHC
SOS phosphorylation and dissociation (SHC)
SOS phosphorylation and dissociation (IRS)
SOS phosphorylation and dissociation (IRS, Crk)
Binding of Grb10 to the insulin receptor
Internalisation of the insulin receptor
Endosome acidification
Dissociation of insulin from insulin receptor
Insulin receptor de-phosphorylation
Re-integration of insulin receptor into plasma membrane
The signal peptide is excised from beta-NGF pre-pro-precursor
pro-beta-NGF dimerizes
pro-beta-NGF homodimer transits to the golgi apparatus
Part of pro-beta-NGF is processed to mature beta-NGF
Pro-beta-NGF and mature beta-NGF are secreted
Binding of pro-NGF to p75NTR:sortilin
NGF homodimer binds to p75NTR
NGF:p75NTR complex binds to NRAGE
NRAGE sequesters CHE1 in the cytoplasm
NRAGE activates JNK
p75NTR indirectly activates RAC and Cdc42 via a guanyl-nucleotide exchange factor
GTP-bound RAC contributes to JNK activation
JNK phosphorylates BIM, BAD and other targets
Active JNK moves to the nucleus and phosphorylates different transcription factors
NRIF binds to p75NTR
TRAF6 binds to p75NTR:NRIF
NRIF and TRAF6 may activate JNK
gamma-secretase cleaves p75NTR, releasing NRIF and TRAF6
TRAF6 polyubiquitinates NRIF
Polyubiquitinated NRIF binds to p62 (Sequestosome)
Polyubiquitinated NRIF migrates to the nucleus
p75NTR binds to NADE
p75NTR:NADE promotes caspase2/3 activation
14-3-3epsilon attentuates NADE-related apoptosis
PRDM4 (SC1) binds to p75NTR
PRDM4 translocates to the nucleus
PRDM4 inhibits cyclin E transcription
p75NTR interacts with RIP2
p75NTR interacts with IRAK:MYD88
IRAK is activated
IRAK interacts with TRAF6
MYD88 dissociates
p62 is recruited and forms a complex with TRAF6
TRAF6 is auto-ubiquitinated
p62 recruits an atypical PKC
IKK-beta is recruited
IKKbeta is activated
IKKbeta phosphorylates IkB causing NF-kB to dissociate
IkB is ubiquitinated and degraded
NF-kB migrates to the nucleus and turns on transcription
Sphingomyelinase is activated by the NGF:p75NTR complex
Production of ceramide which can activate JNK and other targets
p75NTR and RHOA-GDI interact
NGF binding to p75NTR inactivates RHOA
p75NTR interacts with the NOGO receptor
p75NTR:NgR complex interacts with the axonal inhibitor LINGO1
Myelin components can interact with p75NTR:NgR:LINGO1
The p75NTR:NgR:MDGI complex reduces RHOA-GDI activity, displacing RHOA
RhoA is activated by nucleotide exchange and inhibits axonal growth
alpha-secretase cleaves the p75NTR extracellular domain
The p75NTR C-terminal fragment enters endosomes
gamma-secretase cleaves the p75NTR transmembrane domain
p75NTR ICD signals to NF-kB
Part of the ICD migrates to the nucleus
beta-NGF dimer binds to TrkA receptor
The bound receptor dimerizes
TrkA receptor autophosphorylates
Activated TrkA receptor internalizes to endosomes
TRKA activation by adenosine A2a receptor
TRKA activation by PACAP type 1 receptor
SHC binds to the activated TrkA receptor
SHC, complexed with TrkA, is tyrosine-phosphorylated
Phospho-Shc dissociates from the TrkA receptor
Ral-GDS binds to Ras-GTP
Guanine nucleotide exchange on RAL
Activation of SRC by RAL-GTP
Binding and activation of MAP Kinase
MAP kinase activates MAPKAPK2, MAPKAPK3 and MSK1
TRKA recruits RIT and RIN
RIT/RIN are activated
RIT/RIN-GTP binds B-RAF
FRS2 binds to active TrkA receptor
FRS2 is phosphorylated by active TrkA receptor
p-FRS2 binds CRKL
Phospho-Frs2:CrkL engages C3G
(Frs2)C3G stimulates nucleotide exchange on Rap1
(Frs2)Rap1-GTP binds to and activates B-Raf
ARMS:Crk complex binds to active TrkA receptor
ARMS is phosphorylated by active TrkA receptor
Crk's SH3 domain engages C3G
C3G stimulates nucleotide exchange on Rap1
(ARMS)Rap1-GTP binds and activates B-Raf
Binding of PLCG1 to active TrkA receptor
Active PLCG1 dissociates from TrkA receptor
Active TRKA binds IRS1/2
TRKA phosphorylates IRS
Active IRS recruits PI3K to the plasma membrane and activates it
PI3K produces PIP3 and other phosphatidyl inositides
PIP3 binds to RhoA and activates it
STAT3 activation
ERK5 is activated
ERK5 translocates to the nucleus
Formation of clathrin-coated vesicle
Endocytosis (internalization) of clathrin-coated vesicle
Axonal transport of NGF:Trk complexes
Translocation of PDGF from ER to Golgi
Processing of classical PDGFs
Release of novel PDGFs as latent factors
Extracellular processing of novel PDGFs
PDGF binds to extracellular matrix proteins
PDGF dimer binds two receptors simultaneously
Autophosphorylation of PDGF beta receptors
Autophosphorylation of PDGF alpha receptors
Autophosphorylation of PDGF alpha/beta receptors
PI3-kinase binds to the active receptor
PI3K catalyses the phosphorylation of PIP2 to PIP3
PLC-gamma binds to the active receptor
Phosphorylation of PLCgamma by PDGFR
Activated PLC gamma dissociates from the PDGF receptor
SH2 domain of Src binds to the active receptor
Activation of Src
SHP2 binds to the active receptor
GAP binds to PDGF-beta receptors only
Grb2/Sos1 complex binds to the active receptor
Sos-mediated nucleotide exchange of Ras (PDGF receptor:Grb2:Sos)
STAT binds to the active receptor
Crk binds to the active PDGF receptor
p130Cas and C3G bind PDGFR bound Crk
Nck binds to the active PDGF receptor
Grb7 binds to the active PDGF receptor
Homodimerization of VEGF proteins
VEGF-A,B,PLGF bind to VEGFR1 leading to receptor dimerization
VEGF-A,C,D bind to VEGFR2 leading to receptor dimerization
VEGF-C,D bind to VEGFR3 leading to receptor dimerization
NRP-1 forms a ternary complex with VEGF165 and VEGFR1
NRP-2 associates with VEGFR1 forming complexes on cell surface
Processing of SCF isoform 1
Dimerization of sSCF
Interaction of KIT and sSCF
Dimerization of KIT upon SCF binding
Autophosphorylation of KIT
Direct recruitment of PI3K to p-KIT
Synthesis of PIP3 from PIP2 by PI3K
Phosphorylation and activation of VAV1
Activation of RAC1
Interaction of Src family kinases with p-KIT
Phosphorylation of p-KIT on Y900 by Src kinases
GRB2:SOS interacts with p-KIT
SHP2 interacts with p-KIT
Phosphorylation of SHP2 by SFKs
GRB2 is indirectly recruited to p-KIT through SHP2
Indirect recruitment of GAB2 to p-KIT
Phosphorylation of GAB2 by SFKs
Indirect recruitment of PI3K to KIT via p(Y)-GAB2
Activation of RAS by p-KIT bound SOS1
Interaction of other tyrosine kinases with p-KIT
Interaction of other adapter proteins with p-KIT
JAK2 binds to p-KIT
Phosphorylation of JAK2
Recruitment of STATs
Phosphorylation of STATs
Dimerization of STATs
Disassociation and translocation of STATs to the nucleus
PKC alpha interacts with and phosphorylates KIT
Interaction of SHP1 and KIT
SOCS1 as a regulator of KIT signaling
Interaction of APS and p-KIT
Phosphorylation of APS
Recruitment of CBL to KIT
Downregulation of c-Kit signaling by SOCS6
LNK binds to p-KIT and inhibit downstream signaling
PTP-RO interacts with p-c-Kit complex
ERBB3 binds neuregulins
ERBB2 forms heterodimers with ligand-activated ERBB receptors: EGFR, ERBB3 and ERBB4
SRC family kinases phosphorylate ERBB2
Trans-autophosphorylation of p-Y877-ERBB2 heterodimers
Trans-autophosphorylation of ERBB2 heterodimers
SHC1 binds phosphorylated ERBB2 heterodimers
SHC1 phosphorylation by ERBB2 heterodimers
Recruitment of GRB2:SOS1 to p-SHC1 in complex with phosphorylated ERBB2 heterodimers
RAS guanyl-nucleotide exchange mediated by SOS1 in complex with GRB2 and p-SHC1:Phosphorylated ERBB2 heterodimers
GRB2:SOS1 complex binds phosphorylated EGFR:ERBB2 heterodimer
RAS guanyl-nucleotide exchange mediated by SOS1 in complex with GRB2 and phosphorylated EGFR:ERBB2 heterodimers.
GRB2:SOS1 complex binds phosphorylated ERBB4:ERBB2 heterodimers
RAS guanyl nucleotide exchange mediated by SOS1 bound to GRB2 in complex with phosphorylated ERBB4:ERBB2 heterodimers
Binding of PI3K subunit p85 (PIK3R1) to ERBB2:P-ERBB3 heterodimer
Recruitment of PI3K subunit p110 (PIK3CA) by PIK3R1 bound to phosphorylated heterodimer of ERBB2 and ERBB3.
PIP2 to PIP3 conversion by PI3K bound to phosphorylated heterodimer of ERBB2 and ERBB3
Binding of p85 subunit of PI3K (PIK3R1) to p-ERBB2:p-ERBB4 CYT-1 heterodimers
Recruitment of PI3K subunit p110 (PIK3CA) by PIK3R1bound to ERBB2:ERBB4cyt1 heterodimer.
PIP2 to PIP3 conversion by PI3K bound to phosphorylated heterodimer of ERBB2 and ERBB4 CYT1
Binding of GRB2:GAB1 to p-ERBB2:p-EGFR
Binding of PI3K subunit p85 (PIK3R1) to GRB2:GAB1 in complex with phosphorylated heterodimer of ERBB2 and EGFR.
Recruitment of catalytic PI3K subunit p110 (PIK3CA) by PIK3R1 bound to GRB2:GAB1 in complex with phosphorylated heterodimer of ERBB2 and EGFR
PIP2 to PIP3 conversion by PI3K bound to GRB2:GAB1 in complex with phosphorylated heterodimer of ERBB2 and EGFR
PLCG1 binds to p-ERBB2:p-EGFR
Phospholipase C gamma 1 (PLCG1) binds to phosphorylated ERBB2:EGFR heterodimer
PLCG1 phosphorylation by p-EGFR:p-ERBB2
GRB7 binds phosphorylated heterodimer of ERBB2 and ERBB3
ERBB3 binds RNF41 ubiquitin ligase
RNF41 ubiquitinates ERBB3
Self-ubiquitination of RNF41
Phosphorylation of USP8 by P-AKT
Ubiquitinated RNF41 binds P-USP8
Deubiquitination of RNF41 by P-USP8
RNF41 binds neuregulin-activated ERBB3
RNF41 ubiquitinates activated ERBB3
CHIP (STUB1) mediates ubiquitination of ERBB2
CUL5 mediates ubiquitination of ERBB2
MATK (CSK homologous kinase) binds phosphorylated ERBB2
ERBB4 binds NRGs or EGF-like ligands
ERBB4 binds neuregulins or EGF-like ligands
NRGs/EGF-like ligands + ERBB4 => NRGs/EGF-like ligands:ERBB4
Homodimerization of ERBB4
Trans-autophosphorylation of ERBB4 homodimers
ERBB4 forms heterodimers with EGFR
ERBB4 forms heterodimers with ERBB3
SHC1 binds P-ERBB4 isoform dimers
Phosphorylation of SHC1 by ERBB4 homodimers
Recruitment of GRB2:SOS1 to phosphorylated SHC1 in complex with phosphorylated ERBB4 homodimers
RAS guanyl-nucleotide exchange mediated by SOS1 in complex with GRB2 and p-Y349,350-SHC1:p-ERBB4
Binding of p85 subunit of PI3K (PIK3R1) to p-ERBB4cyt1 homodimers
Recruitment of PI3K subunit p110 (PIK3CA) to PI3K subunit p85 (PIK3R1) bound to p-ERBB4cyt1 homodimers
Conversion of PIP2 into PIP3 by PI3K bound to p-ERBB4cyt1 homodimers
Cleavage of P-ERBB4jmA isoforms by ADAM17
Cleavage of ERBB4m80 by gamma-scretase complex
Translocation of ERBB4s80 to the nucleus
ERBB4s80 binds TAB2:NCOR1 complex
ERBB4:TAB2:NCOR1 complex translocates to the nucleus
Transcription of GFAP and S100B
WWOX binds ERBB4s80
ERBB4s80 binds YAP1
Translocation of ERBB4s80:YAP1 complex to the nucleus
ERBB4s80 binds STAT5A
ERBB4s80:STAT5A complex translocates to the nucleus
ERBB4s80 forms a complex with estrogen receptor ESR1
Transcription of NR3C3 and CXCL12
Translocation of cytosolic ERBB4s80 to mitochondrial matrix
ERBB4 binds WWP1/ITCH ubiquitin ligases
ERBB4 ubiquitination by WWP1/ITCH
NEDD4 binds ERBB4jmAcyt1s80 dimer
NEDD4 ubiquitinates ERBB4jmAcyt1s80 dimer
GEFs activate Rho GTPase:GDP
Rho GTPase:GTP activates downstream effectors
GAPs inactivate Rho GTPase:GTP by hydrolysis
GDIs block activation of Rho GTPase:GDP
Dissociation of Rho GTP:GDP from GDI complex
The ligand trap binds the ligand BMP2, blocking BMP signalling
Formation of a heteromeric BMP receptor complex
BMP2 binds to the receptor complex
Type II receptor phosphorylates type I receptor
An anchoring protein, Endofin, recruits R-Smad1/5/8
I-Smad binds to type I receptor, preventing Smad1/5/8 from being activated
Activated type I receptor phosphorylates R-Smad1/5/8 directly
Phospho-R-Smad1/5/8 dissociates from the receptor complex
I-Smad competes with Co-Smad for R-Smad1/5/8
Phospho-R-Smad1/5/8 forms a complex with Co-Smad
The phospho-R-Smad1/5/8:Co-Smad transfers to the nucleus
SKI complexes with the Smad complex, suppressing BMP2 signalling
I-Smad competes with R-Smad1/5/8 for type I receptor
Latent TGF-beta-1 is cleaved by furin
Secretion and activation of the latent large complex of TGF-beta-1
Dimeric TGF-beta-1 binds to the receptor
Dimeric TGFB1 binds to TGFBR2 homodimer
TGFBR2 recruits TGFBR1
Type II receptor recruits type I receptor
TGFBR2 phosphorylates TGFBR1
An anchoring protein, SARA, recruits SMAD2/3
Activated type I receptor phosphorylates SMAD2/3 directly
Phosphorylated SMAD2/3 dissociates from TGFBR
I-SMAD competes with SMAD2/3 for type I receptor (TGFBR1)
STRAP binds phosphorylated TGF-beta receptor complex
STRAP binds unphosphorylated TGF-beta receptor complex
STRAP stabilizes interaction of activated TGF-beta receptor complex with SMAD7
BAMBI interferes with the interaction of type I receptor with type II receptor
SMAD7 recruits GADD34:PP1 to phosphorylated TGFBR
PP1 dephosphorylates TGFBR1
SMAD7 binds to SMURF2
SMAD7:SMURF2 complex translocates to the cytosol
SMAD7 binds to SMURF1
SMAD7:SMURF1 complex binds XPO1 (CRM1)
SMAD7:SMURF1 complex is exported to the cytosol
NEDD4L ubiquitin ligase binds SMAD7
SMAD7:NEDD4L complex translocates to the cytosol
SMAD7:SMURF complex binds to phosphorylated TGFBR1
SMURFs/NEDD4L ubiquitinate phosphorylated TGFBR1 and SMAD7
UCHL5 binds SMAD7 in complex with ubiquitinated TGFBR1
UCHL5 or USP15 deubiquitinates TGFBR1
SMURF2 binds SMAD2
SMURF2 ubiquitinates SMAD2
SMAD3 binds STUB1 (CHIP)
STUB1 (CHIP) ubiquitinates SMAD3
PMEPA1 sequesters phosphorylated SMAD2/3
PMEPA1 sequesters unphosphorylated SMAD2/3
MTMR4 binds phosphorylated SMAD2/3
MTMR4 dephosphorylates SMAD2/3
TGFBR1 is recruited to tight junctions by PARD6A
TGFBR2 is recruited to tight junctions after TGF-beta stimulation
TGFBR2 phosphorylates TGFBR1 and PARD6A
SMURF1 binds phosphorylated PARD6A
SMURF1 ubiquitinates RHOA
Disassembly of tight junctions
NOTCH1 gene transcription
NOTCH2 gene transcription
NOTCH3 gene transcription
NOTCH4 gene transcription
p53 positively regulates transcription of MIR34 microRNAs
MIR34 microRNAs bind 3'UTR of NOTCH1 mRNA
MIR200B/C microRNAs bind NOTCH1 mRNA
MIR449 microRNAs bind 3'UTR of NOTCH1 mRNA
MIR34 microRNAs bind 3'UTR of NOTCH2 mRNA
MIR150 microRNA binds 3'UTR of NOTCH3 mRNA
MIR206 microRNA binds 3'UTR of NOTCH3 mRNA
MIR181C microRNA binds 3'UTR of NOTCH4 mRNA
MIR302A microRNA binds 3'UTR of NOTCH4 mRNA
NOTCH1 mRNA translation controlled by miRNAs
NOTCH2 mRNA translation controlled by miRNAs
NOTCH3 mRNA translation controlled by miRNAs
NOTCH4 mRNA translation controlled by miRNAs
Fucosylation of Pre-NOTCH by POFUT1
Glucosylation of Pre-NOTCH by POGLUT1
Transport of NOTCH precursor to Golgi
NOTCH precursor cleaved to form mature NOTCH
Glycosylation of Pre-NOTCH by FRINGE
Galactosylation of Pre-NOTCH
Sialylation of Pre-NOTCH
Fringe-modified Pre-NOTCH is cleaved by FURIN
Mature NOTCH heterodimer traffics to the plasma membrane
Transport of fringe-modified NOTCH to plasma membrane
DLL1 binds NOTCH2
JAG1 binds NOTCH2
JAG2 binds NOTCH2
DLL4 binds NOTCH2
Ubiquitination of DLL/JAG ligands upon binding to NOTCH2
NOTCH2 binds CNTN1
Gamma-secretase cleaves CNTN1:NOTCH2 to release NICD2
NOTCH2 binds MDK
NICD2 binds RBPJ and MAML in the nucleus
NOTCH2 coactivator complex binds HES1 promoter
NOTCH2 stimulates HES1 transcription
NOTCH2 coactivator complex binds HES5 promoter
NOTCH2 stimulates transcription of HES5
NOTCH2 coactivator complex binds FCER2 promoter
NOTCH2 stimulates transcription of FCER2 (CD23A)
NOTCH2 coactivator complex and phosphorylated CREB1 bind GZMB promoter
NOTCH2 stimulates GZMB transcription
Notch 3 heterodimer binds with a Notch ligand in the extracellular space
Notch 4 heterodimer binds with a Notch ligand in the extracellular space
Angiotensin II binds to angiotensin II receptor (types 1 and 2)
Apelin receptor binds to apelin
Bombesin-like receptors bind bombesin homologues
Bradykinin receptors B1 and B2 bind to bradykinin
GPR77 binds anaphylatoxins and thier desArginated derivatives
C5a receptor binds C5a anaphylatoxin
C3a receptor binds anaphylatoxin C3a
DARC is a non-specific receptor for many chemokines
G protein-coupled estrogen receptor 1 binds estrogen non-classically
GPCR neuropeptide receptor binds neuropeptides B and W
Nociceptin receptor binds to nociceptin
Opioid receptors bind opioid peptides
Receptor CCR10 binds CCL27 and 28 ligands
Receptor CCR6 binds CCL20 ligand
Receptor CCR7 binds CCL19 and 21 ligands
Receptor CCR9 binds CCL25 ligand
Receptor CX3C1 binds CX3CL1
Receptor CXC1 binds to the ligands lymphotactin and cytokine SCM-1 beta
Receptor CXCR1 binds CXCL6 and CXCL8 ligands
Receptor CXCR2 binds ligands CXCL1 to 7
Receptor CXCR3 binds ligands CXCL9 to 11
Receptors CXCR4 and 7 bind CXCL12 ligand
CXCR5 binds CXCL13
Receptor CXCR6 binds CXCL16 ligand
Receptors CCR1, 2 and 8 bind CCL16 ligand
Receptors CCR3, 4 and 5 bind CCL5 ligand
Receptor CCBP2 binds most inflammatory CC chemokines
Receptor CCR11 binds CCL19, CCL21 & CCL25
CCRL2 binds CCL19
Somatostatin receptors bind somatostatin
Tachykinin receptor 1 (NK1) binds to substance P
Tachykinin receptor 2 (NK2) binds to nuerokinin A
Tachykinin receptor 3 (NK3) binds to neurokinin B
Vasopressin receptor type 1 bind vasopressin
Oxytocin receptor bind oxytocin
Cholecystokinin receptors bind cholecystokinin
Endothelin receptors bind endothelin
Melanocortin receptors bind melanocortins
ACTH specifically binds with melanocortin receptor 2
Prolactin-releasing hormone receptor binds PRH
Neuropeptide Y receptors can bind neuropeptide Y-related peptides
Neurotensin receptors can bind neurotensins
Galanin receptors can bind galanin
The Kiss receptor GPR54 binds kisspeptin
Proteinase-activated receptors can bind thrombin
Orexin 1 receptor can bind orexin-A neuropeptide
Orexin 2 receptor can bind orexin-B neuropeptide
Two NPFF receptors can bind neuropeptide FF
The orphan QRFP receptor can bind neuropeptide QRFP
MLNR (GPR38) is a receptor for motilin
FPR is a receptor for formyl peptides
FPRL1 receptor binds a wide range of ligands
FPRL2 receptor binds a wide range of ligands
Thyrotropin-releasing hormone receptor binds thyrotropin
Neuropeptide S receptor binds neuropeptide S
Prokineticin receptors bind prokineticin
Relaxin receptor 1 binds relaxin 2 and 3
Relaxin receptor 2 binds relaxin 2 and INSL3
Relaxin 3 receptor 1 binds relaxin 3
Relaxin 3 receptor 2 binds relaxin 3 and INSL5
Urotensin-2 receptor binds urotensin-2 and 2B
GHSR is a receptor for ghrelin
Melanin-concentrating hormone receptors bind MCH
Neuromedin-U receptors bind neuromedins U, S
NMUR2 binds neuromedin-S
M2 and M4 receptors bind acetylcholine
M1, M3 and M5 receptors bind acetylcholine
Alpha-1 adrenoceptors bind catecholamines
Beta adrenoceptors bind catecholamines
D1-like dopamine receptors bind to dopamine
D2-like dopamine receptors bind to dopamine
H1 receptor binds histamine
H2 receptor binds histamine
H3 and H4 receptors binds histamine
5-HT1 and 5A receptors can bind serotonin
5-HT2 receptor can bind serotonin
5-HT4, 6 and 7 receptors can bind serotonin
Trace amine-associated receptors can bind trace amines
Follicle-stimulating hormone receptor can bind FSH
Gonadotropin-releasing hormone receptors can bind GNRH I and II
Luteinizing hormone receptor can bind LH
Thyroid-stimulating hormone receptor can bind TSH
EP1 receptor can bind PGE2
EP2 and EP4 receptors can bind PGE2
EP3 receptor can bind PGE2
FP receptor can bind PGF2-alpha
IP receptor can bind prostacyclin
DP1 receptor can bind PGD2
DP2 receptor can bind PGD2
BLT receptors can bind LTB4
CysLT receptors can bind cysteinyl leukotrienes
UDP/CysLT receptor can bind cysteinyl leukotrienes
Oxoeicosanoid receptor can bind oxoeicosanoid
P2Y1 receptor can bind to ADP
P2Y2 receptor binds ATP and UTP
P2Y4 receptor can bind to UTP
P2Y5 receptor can bind to LPA
P2Y6 receptor can bind to UDP
P2Y9 receptor can bind to LPA
P2Y10 receptor can bind to LPA
P2Y11 receptor can bind to ATP
P2Y12 receptor can bind to ADP
P2Y13 receptor can bind ADP
P2Y14 receptor can bind to UDP-glucose
The UDP/CysLT (P2Y17) receptor can bind UTP
A1 and A3 receptors bind adenosine
A2a and A2b receptors bind adenosine
HCAR2 binds HCAR2 ligands
HCAR1 binds L-lactate
HCAR1 binds LACT
HCAR3 binds HCAR3 ligands
Cannabinoid receptors can bind cannabinoids
PAF receptor binds platelet activating factor
Melatonin receptors can bind melatonin
LPA-binding receptors bind LPA
S1P-binding receptors bind S1P
Light stimulates opsin receptors
Melanospin is stimulated by light
Receptor FFAR1 binds free fatty acids
Receptor FFAR2 binds carboxylates
Receptor FFAR3 binds carboxylates
GPR120 is a receptor for unsaturated long-chain free fatty acids
GPR31 is a receptor for 12(S)-HETE
GPR4, GPR65, GPR132 and OGR1 are pH sensing receptors
G-protein coupled bile acid receptor binds lithocholic acid
N-arachidonyl glycine receptor GPR18 binds N-arachidonyl glycine
Zinc is an agonist of GPR39
OXGR1 binds 2OG
SUCNR1 binds SUCCA
SUCNR1 binds succinate
Calcitonin receptor binds calcitonin
Amylin receptors can bind Amylin
CGRP receptor can bind calcitonin gene-related peptides
The adrenomedullin receptor can bind adrenomedullin and intermedin
Corticotropin-releasing hormone receptor can bind CRH
GIP receptor binds gastric inhibitory peptide
Glucagon binds to Glucagon receptor
Binding of Glucagon-like Peptide-1 by Glucagon-like Peptide-1 Receptor
Glucagon-like receptor 2 binds GLP2
GHRH receptor binds GHRH
The PACAP receptor binds PACAP
Secretin receptor binds secretin
Parathyroid hormone receptor can bind parathyroid hormone
Patched binds Smoothened
Frizzled receptors bind Wnts
EGF-TM7 receptors bind chondroitin sulphate
CD97 binds CD55
Metabotropic glutamate receptors bind glutamate
Calcium-sensing receptor binds calcium
GPRC6A can bind L-alpha amino acids and calcium
T1R1/T1R3 dimer is the umami taste receptor
T1R2/T1R3 dimer is a sweet taste receptor
T2Rs bind bitter-tasting compounds
Liganded Gs-activating GPCRs bind inactive heterotrimeric Gs
Liganded Gs-activating GPCR acts as a GEF for Gs
The Ligand:GPCR:Gs complex dissociates
Adenylate cyclase converts ATP to 3',5'-cyclic AMP (cAMP) and pyrophosphate
cAMP degradation by Phosphodiesterases
G alpha (s) auto-inactivates by hydrolysing GTP to GDP
Inactive G alpha (s) reassociates with G beta:gamma
Liganded Gi-activating GPCRs bind inactive heterotrimeric G-protein Gi
Liganded Gi-activating GPCR acts as a GEF for Gi
The Ligand:GPCR:Gi complex dissociates
Opsins that act as GEFs for G alpha-t
G alpha (i) auto-inactivates by hydrolysing GTP to GDP
Inactive G alpha (i) reassociates with G beta:gamma
Liganded Gz-activating GPCRs bind inactive heterotrimeric G-protein Gz
Liganded Gz-activating GPCR acts as a GEF for Gz
The Ligand:GPCR:Gz complex dissociates
G alpha (z) inhibits adenylate cyclase
Gz is a substrate for PKC
G alpha (z) auto-inactivates by hydrolysing GTP to GDP
Inactive G alpha (z) reassociates with G beta:gamma
Liganded Gq-activating GPCRs bind inactive heterotrimeric Gq
Liganded Gq/11-activating GPCRs act as GEFs for Gq/11
The Ligand:GPCR:Gq complex dissociates
GRK2 sequesters activated Gq
GRK5 sequesters activated Gq
G alpha (q) binds to Trio family RhoGEFs
PLC beta is activated by G alpha (q)
G alpha (q) inhibits PI3K alpha
PLC beta-mediated PIP2 hydrolysis
G alpha (q) auto-inactivates by hydrolysing GTP to GDP
Inactive G alpha (q) reassociates with G beta:gamma
Liganded G12/13-activating GPCRs bind inactive heterotrimeric G-protein G12/13
Liganded G12/13-activating GPCR acts as a GEF for G12/13
The Ligand:GPCR:G12/13 complex dissociates
G alpha (13) activates Rho guanine nucleotide exchange factor 1 (p115-RhoGEF)
p115-RhoGEF activation of Rac1
Rac1 activation of PI3K
GEFs activate RhoA,B,C
ROCK activation by Rho
LARG activation by G alpha 12/13
LARG binds plexin B1
G alpha (12/13) auto-inactivates by hydrolysing GTP to GDP
Inactive G alpha (12/13) reassociates with G beta:gamma
Gbeta:gamma recruits PI3K gamma
G beta:gamma activated PI3Kgamma converts PIP2 to PIP3
Gbeta:gamma activation of PLC beta
G Protein trimer formation (olfactory)
Olfactory Receptor - G Protein olfactory trimer complex formation
Opioid binds MOR
The high affinity receptor complex binds to G-protein
The receptor:G-protein complex releases GDP
The receptor:G-protein complex binds GTP
The receptor:G-protein complex dissociates
G-protein alpha subunit is inactivated
G-protein beta-gamma subunits rebind the alpha-GDP subunit
Opioid dissociates from MOR
Activation of PLC beta-1/4
PIP2 hydrolysis
Inactivation of PLC beta
Phosphorylation of cPLA2 by ERK-2
Phospho-cPLA2 translocates to membranes when intracellular calcium levels increase
Hydrolysis of phosphatidylcholine
Galpha-olf:GTP binds to adenylate cyclase and activates it
Adenylate cyclase converts ATP into cyclic AMP
Adenylaye cyclase increases the GTPase activity of G alpha-olf
The G alpha-olf:GDP:Adenylate cyclase complex dissociates
PKA phosphorylates PDE4B
cAMP hydrolysis by PDE 4
PKA phosphorylates DARPP-32 on Thr34
DARPP-32 phosphorylated on T34 binds to PP1, inhibiting its function
CDK5 phosphorylates DARPP-32 on Thr75
DARPP-32 phosphorylated on Thr75 binds to PKA, inhibiting its function
DARPP-32 is dephosphorylated on Thr75 by PP2A
Inactive catalytic PP2B is activated by the binding of calmodulin
DARPP-32 is dephosphorylated on Thr34 by PP2B
Gastrin binds to CCK-B receptor
Activation of Protein kinase C, alpha type by Diacylglycerol
Active MMP3 can cleave pro-HBEGF to form active HBEGF
Mature HBEGF binds to EGFR, triggering dimerisation and autophosphorylation of the receptor
GRB2:SOS1 binds to HBEGF:p-Y-EGFR
SOS1-mediated nucleotide exchange of RAS (HB-EFG-initiated)
N-linked glycosylation of WNTs
PORCN palmitoleoylates N-glycosyl WNTs
WNT ligands traffic to the Golgi
WLS binds WNT ligands in the Golgi
WNT ligands traffic to the plasma membrane
secretion of WNT ligands
WLS is endocytosed to the early endosome
Retromer associates with WLS
Retromer recycles WLS to the Golgi
WLS dissociates from retromer
Assembly of the destruction complex
Association of beta-catenin with the destruction complex
Phosphorylation of beta-catenin at Ser45 by CK1 alpha
Phosphorylation of phospho-(Ser45 ) at Thr 41 by GSK-3
Phosphoryation of phospho- (Ser45, Thr41) beta-catenin at Ser37 by GSK-3
Phosphorylation of phospho-(Ser45,Thr41,Ser37) at Ser33 by GSK-3
Phosphorylation of APC component of the destruction complex
Dissociation of beta-catenin from Axin and association of beta catenin with phospho-(20 aa) APC in the detruction complex
Association of beta-catenin with the SCF-beta-TrCP1 ubiquitin ligase complex
Multi-ubiquitination of phospho-beta-catenin by SCF-beta-TrCP1
Degradation of ubiquitinated -beta catenin by the proteasome
Phosphorylation of STK3 (MST2) and SAV1 by STK3
Phosphorylation of STK4 (MST1) and SAV1 by STK4
Cleavage of p-STK3 (p-MST2) by caspase 3
Cleavage of p-STK4 (p-MST1) by caspase 3
KIBRA (WWC1) binds LATS proteins
NPHP4 protein binds LATS proteins
Phosphorylation of LATS1 and 2 by p-STK3 (p-MST2)
Phosphorylation of LATS1 and 2 by p-STK3 (MST2)/N
Phosphorylation of LATS1 and 2 by p-STK4 (p-MST1)
Phosphorylation of LATS1 and 2 by p-STK4(MST1)/N
Phosphorylation of MOB1A and B by p-STK3 (p-MST2)
Phosphorylation of MOB1A and B by p-STK3(MST2)/N
Phosphorylation of MOB1A and B by p-STK4 (p-MST1)
Phosphorylation of MOB1A and B by p-STK4(MST1)/N
Phosphorylated MOB1A proteins associate with LATS proteins
Translocation of YAP1 to the nucleus
YAP1 binds ZO-2 (TJP2)
Translocation of YAP1:ZO-2 (TJP2) to the nucleus
AMOT proteins bind YAP1
Phosphorylation of YAP by LATS1
Phosphorylation of YAP by LATS2
YWHAB (14-3-3 beta/alpha) dimer binds phosphorylated YAP1
Translocation of WWTR1 (TAZ) to the nucleus
WWTR1 (TAZ) binds ZO-1 (TJP1)
WWTR1 (TAZ) binds ZO-2 (TJP2)
AMOT proteins bind WWTR1 (TAZ)
Phosphorylation of WWTR1 (TAZ) by LATS1
Phosphorylation of WWTR1 (TAZ) by LATS2
DVL2 binds phosphorylated WWTR1 (TAZ)
YWHAE (14-3-3 epsilon) dimer binds phosphorylated WWTR1 (TAZ)
Interaction of integrin alpha1beta1 with Type IV collagen
Interaction of integrin alpha1beta1 with Laminin-1
Interaction of integrin alpha2beta1 with Lamini-5
Interaction of integrin alpha3beta1 with Laminin-5
Interaction of integrin alpha3beta1 with Thrombospondin-1
Interaction of integrin alpha4beta1 with Fibronectin
Interaction of integrin alpha4beta1 with Thrombospondin-1
Interaction of integrin alpha4beta1 with Osteopontin
Interaction of integrin alpha5beta1 with Osteopontin
Interaction of integrin alpha6beta1 with Laminin-1
Interaction of integrin alpha6beta4 with Laminin-5
Interaction of integrin alpha7beta1 with Laminin-1
Interaction of integrin alpha7beta1 with Laminin-2
Interaction of integrin alpha8beta1 with Fibronectin
Interaction of integrin alpha8beta1 with Osteopontin
Interaction of integrin alpha8beta1 with Tenascin-c
Interaction of integrin alpha9beta1 with Osteopontin
Interaction of integrin alpha9beta1 with VCAM-1
Interaction of integrin alpha9beta1 with tenascin
Interaction of integrin alpha10beta1 with Collagen-II
Interaction of integrin alpha11beta1 with Collagen-I
Interaction of integrin alphaDbeta2 with fibrin
Interaction of integrin alphaVbeta1 with FN1
Interaction of integrin alphaVbeta5 with vitronectin
Interaction of integrin alphaVbeta6 with Fibronectin
Interaction of integrin alphaVbeta8 with vitronectin
Interaction of integrin alphaXbeta2 with fibrin
Interaction of integrin alphaVbeta3 with Bone sialoprotein 2
Interaction of integrin alphaVbeta3 with vitronectin
Interaction of integrin alphaVbeta3 with Fibronectin
Interaction of integrin alphaVbeta3 with Tenascin
Interaction of integrin alphaVbeta3 with Fibrillin
Interaction of integrin alphaVbeta3 with von Willbrand Factor
Interaction of integrin alphaEbeta7 with Cadherin-1
Interaction of integrin alphaIIbbeta3 with Fibronectin
Adhesion of integrin alphaIIbbeta3 to fibrin network
Interaction of integrin alphaIIbbeta3 with von Willebrand factor
Interaction of integrin alphaIIb beta 3 with Thrombospondin
IGF1/2 binds IGF1R
Autophosphorylation of IGF1R
Binding of SHC1 by phosphorylated IGF1R
Phosphorylation of SHC1 by IGF1R
IGF1/2:p-IGF1R binds IRS1/4
IGF1/2:p-IGF1R binds IRS2
IGF1/2:p-IGF1R phosphorylates IRS1/2/4
Activin A/AB/B Binds Activin Receptor ACVR2A/B:ACVR1B
Activin AB/B Binds Activin Receptor ACVR2A/B:ACVR1C
ACVR2A/B (ActRIIA/B) Phosphorylates ACVR1B (ActRIB, ALK4) in Response to Activin
ACVR2A/B (ActRIIA/B) Phosphorylates ACVR1C (ActRIC, ALK7) in Response to Activin
Phosphorylation of SMAD2/3 by Activin:Activin Receptor
Phospho R-SMAD(SMAD2/3):CO-SMAD(SMAD4):FOXH1 Binds Activin Response Element
FSTL3 binds Activin
Follistatin (FST) binds Activin
PIP3 recruits PDPK1 to the membrane
PIP3 recruits AKT to the membrane
TORC2 (mTOR) phosphorylates AKT at S473
AKT binds PDPK1
PDPK1 phosphorylates AKT at T308
IP3 binds to the IP3 receptor, opening the endoplasmic reticulum Ca2+ channel
Release of calcium from intracellular stores by IP3 receptor activation
PI3K phosphorylates PIP2 to PIP3
AKT phosphorylates BAD
AKT phosphorylates GSK3
AKT phosphorylates caspase-9
AKT phosphorylates MDM2
AKT phosphorylates IKKalpha
AKT phosphorylates p21Cip1 and p27Kip1
AKT phosphorylates TSC2, inhibiting it
AKT phosphorylates AKT1S1 (PRAS40)
AKT translocates to the nucleus
AKT phosphorylates CREB1
AKT can phosphorylate forkhead box transcription factors
AKT can phosphorylate RSK
AKT can phosphorylate NR4A1 (NUR77)
PTEN dephosphorylates PIP3
THEM4 (CTMP) and/or TRIB3 inhibit AKT phosphorylation
PHLPP dephosphorylates S473 in AKT
PDPK1 binds PIP2
MIR26A microRNAs bind PTEN mRNA
PTEN mRNA translation negatively regulated by microRNAs
VCAM-1interacts with VLA-4
MADCAM interacts with Integrin alpha4beta7
ICAMs 1-4 bind to Integrin LFA-1
Activation of Rap1 by membrane-associated GEFs
Activation of Rap1 by cytosolic GEFs
Inactivation of MEK1 by p34cdc2
MEK1 binds ERK-1
MEK1 phosphorylates ERK-1
Dissociation of phospho-ERK-1:MEK1
Dimerisation of phospho-ERK-1
Nuclear translocation of phospho-ERK-1 dimer
MEK2 binds ERK-2
MEK2 phosphorylates ERK-2
Dissociation of phospho-ERK-2:MEK2
Dimerisation of phospho-ERK-2
Nuclear translocation of phospho-ERK-2 dimer
ERK1/2 activates ELK1
ERK1/2 phosphorylates MSK1
p38MAPK phosphorylates MSK1
ERK1/2/5 activate RSK1/2/3
ERK5 activates the transcription factor MEF2
ERKs are inactivated by protein phosphatase 2A
ERKs are inactivated by dual-specific phosphatases (DUSPs)
MSK1 activates CREB
MSK1 activates ATF1
RSK1/2/3 phosphorylates CREB at Serine 133
MAPKAPK2 phosphorylates CREB at Serine 133
Degradation of Ub-SMAD7
Insulin degradation
Ubiquitin-dependent degradation controls basal levels of R-Smad1/5/8
Ubiquitin-dependent degradation of the Smad complex terminates BMP2 signalling
Degradation of TGF-beta receptor complex
Degradation of ubiquitinated SMAD2
Degradation of ubiquitinated SMAD3
Degradation of ubiquitinated SKI/SKIL
Degradation of SMAD2/3:SMAD4 complex
Ubiquitin-dependent degradation of the SMAD complex terminates TGF-beta signaling
p75NTR regulates axonogenesis
Axonal growth stimulation
Axonal growth inhibition (RHOA activation)
Regulated proteolysis of p75NTR
NGF signalling via TRKA from the plasma membrane
Activation of TRKA receptors
TRKA activation by NGF
NGF-independant TRKA activation
Signalling to ERKs
Signalling to RAS
Feedback control in the MAPK signaling module
p38MAPK events
Signalling to p38 via RIT and RIN
Prolonged ERK activation events
Frs2-mediated activation
ARMS-mediated activation
PLC-gamma1 signalling
PI3K/AKT activation
Signalling to STAT3
Signalling to ERK5
Retrograde neurotrophin signalling
Nuclear Events (kinase and transcription factor activation)
Signaling by PDGF
Downstream signal transduction
Signaling by VEGF
Signaling by Vascular Epithelial Growth Factors (VEGF)
VEGF ligand-receptor interactions
VEGF binds to VEGFR leading to receptor dimerization
Neurophilin interactions with VEGF and VEGFR
Signaling by SCF-KIT
Regulation of KIT signaling
Signaling by ERBB2
SHC1 events in ERBB2 signaling
GRB2 events in ERBB2 signaling
PI3K events in ERBB2 signaling
PLCG1 events in ERBB2 signaling
GRB7 events in ERBB2 signaling
Downregulation of ERBB2:ERBB3 signaling
Signaling by ERBB4
SHC1 events in ERBB4 signaling
PI3K events in ERBB4 signaling
Nuclear signaling by ERBB4
Downregulation of ERBB4 signaling
Signaling by Rho GTPases
Rho GTPase cycle
Signaling by BMP
Signaling by TGF-beta Receptor Complex
Transforming Growth Factor (TGF) beta signaling
TGF-beta receptor signaling activates SMADs
Downregulation of TGF-beta receptor signaling
TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition)
NOTCH Signaling Pathway
Signaling by NOTCH
Pre-NOTCH Expression and Processing
Pre-NOTCH Transcription and Translation
Pre-NOTCH Processing in the Endoplasmic Reticulum
Pre-NOTCH Processing in Golgi
Signaling by NOTCH2
NOTCH2 Activation and Transmission of Signal to the Nucleus
NOTCH2 intracellular domain regulates transcription
Signaling by NOTCH3
Signaling by NOTCH4
Signaling by GPCR
GPCR ligand binding
Class A/1 (Rhodopsin-like receptors)
Peptide ligand-binding receptors
Chemokine receptors bind chemokines
Tachykinin receptors bind tachykinins
Vasopressin-like receptors
Orexin and neuropeptides FF and QRFP bind to their respective receptors
Formyl peptide receptors bind formyl peptides and many other ligands
Relaxin receptors
Amine ligand-binding receptors
Muscarinic acetylcholine receptors
Adrenoceptors
Dopamine receptors
Histamine receptors
Serotonin receptors
Hormone ligand-binding receptors
Eicosanoid ligand-binding receptors
Prostanoid ligand receptors
Leukotriene receptors
Nucleotide-like (purinergic) receptors
P2Y receptors
Adenosine P1 receptors
Hydroxycarboxylic acid-binding receptors
Lysosphingolipid and LPA receptors
Opsins
Free fatty acid receptors
Class B/2 (Secretin family receptors)
Calcitonin-like ligand receptors
Glucagon-type ligand receptors
Class C/3 (Metabotropic glutamate/pheromone receptors)
GPCR downstream signaling
G alpha (s) signalling events
G alpha (i) signalling events
G alpha (z) signalling events
G alpha (q) signalling events
G alpha (12/13) signalling events
G-protein beta:gamma signalling
G beta:gamma signalling through PI3Kgamma
G beta:gamma signalling through PLC beta
Olfactory Signaling Pathway
Opioid Signalling
G-protein activation
G-protein mediated events
PLC beta mediated events
Ca-dependent events
phospho-PLA2 pathway
Adenylate cyclase activating pathway
DARPP-32 events
Gastrin-CREB signalling pathway via PKC and MAPK
EGFR Transactivation by Gastrin
Signaling by Wnt
WNT ligand biogenesis and trafficking
Degradation of beta-catenin by the destruction complex
Beta-catenin phosphorylation cascade
Hippo signaling cascade
Signaling by Hippo
Integrin cell surface interactions
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)
IGF1R signaling cascade
SHC-related events triggered by IGF1R
IRS-related events triggered by IGF1R
Signaling by Activin
Antagonism of Activin by Follistatin
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer
SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription
Downregulation of SMAD2/3:SMAD4 transcriptional activity
PIP3 activates AKT signaling
AKT phosphorylates targets in the cytosol
AKT phosphorylates targets in the nucleus
Negative regulation of the PI3K/AKT network
ERK activation
ERK1 activation
ERK2 activation
ERK/MAPK targets
ERKs are inactivated
CREB phosphorylation
RAF/MAP kinase cascade
RAF activation
MEK activation
RAF phosphorylates MEK
DAG and IP3 signaling
CaM pathway
Calmodulin induced events
PKA-mediated phosphorylation of CREB
PKA activation
CaMK IV-mediated phosphorylation of CREB
Cam-PDE 1 activation
Prolactin receptor signaling
Integrin alphaIIb beta3 signaling
GRB2:SOS provides linkage to MAPK signaling for Intergrins
p130Cas linkage to MAPK signaling for integrins
Effects of PIP2 hydrolysis
Arachidonate production from DAG
Epidermal Growth Factor Receptor (EGFR) signaling
Signaling by EGFR
EGFR interacts with phospholipase C-gamma
GRB2 events in EGFR signaling
SHC1 events in EGFR signaling
GAB1 signalosome
EGFR downregulation
Fibroblast Growth Factor Receptor (FGFR) signaling
Signaling by FGFR
FGFR ligand binding and activation
FGFR1 ligand binding and activation
FGFR1b ligand binding and activation
FGFR1c ligand binding and activation
FGFR2 ligand binding and activation
FGFR2b ligand binding and activation
FGFR2c ligand binding and activation
FGFR3 ligand binding and activation
FGFR3b ligand binding and activation
FGFR3c ligand binding and activation
FGFR4 ligand binding and activation
Klotho-mediated ligand binding
betaKlotho-mediated ligand binding
FGFR1c and Klotho ligand binding and activation
Downstream signaling of activated FGFR
FRS2-mediated cascade
Phospholipase C-mediated cascade
SHC-mediated cascade
PI-3K cascade
Negative regulation of FGFR signaling
Spry regulation of FGF signaling
Visual phototransduction
Retinoid metabolism and transport
The canonical retinoid cycle in rods (twilight vision)
The retinoid cycle in cones (daylight vision)
The phototransduction cascade
Activation of the phototransduction cascade
Inactivation, recovery and regulation of the phototransduction cascade
Signaling by NOTCH1
Activated NOTCH1 Transmits Signal to the Nucleus
NOTCH1 Intracellular Domain Regulates Transcription
Adenylate cyclase inhibitory pathway
Signal Transduction
Signaling Pathways
Insulin receptor mediated signaling
Signaling by Insulin receptor
Insulin receptor signalling cascade
SHC-related events
SHC activation
SHC-mediated signalling
IRS-related events
IRS activation
IRS-mediated signalling
PI3K Cascade
PKB-mediated events
PDE3B signalling
mTOR signalling
Inhibition of TSC complex formation by PKB
mTORC1-mediated signalling
S6K1-mediated signalling
S6K1 signalling
Release of eIF4E
Energy dependent regulation of mTOR by LKB1-AMPK
Regulation of AMPK activity via LKB1
Regulation of Rheb GTPase activity by AMPK
Activation of PKB
SOS-mediated signalling
Signal attenuation
Insulin receptor recycling
Nerve Growth Factor (NGF) signalling
Signaling by NGF
Signalling by NGF
NGF processing
p75 NTR receptor-mediated signalling
NFG and proNGF binds to p75NTR
Cell death signalling via NRAGE, NRIF and NADE
NRAGE signals death through JNK
NRIF signals cell death from the nucleus
NADE modulates death signalling
p75NTR negatively regulates cell cycle via SC1
p75NTR signals via NF-kB
p75NTR recruits signalling complexes
NF-kB is activated and signals survival
Ceramide signalling
Transcription of beta-casein (CSN2)
Activated PKC-alpha can activate MMP3
NOTCH1 stimulates HES1 transcription
NOTCH1 stimulates MYC transcription
NOTCH1 stimulates HES5 transcription
NOTCH1 stimulates HEY transcription