MSK1
RPS6KA5
UniProt:O75582 RPS6KA5
DNAL4
UniProt:O96015 DNAL4
CDC2
CDC28A
CDK1
CDKN1
P34CDC2
UniProt:P06493 CDK1
SRC
SRC1
UniProt:P12931-1 SRC
PLC1
PLCG1
UniProt:P19174 PLCG1
ADORA2
ADORA2A
UniProt:P29274 ADORA2A
ADCYAP1R1
UniProt:P41586 ADCYAP1R1
JNK1
MAPK8
PRKM8
SAPK1
SAPK1C
UniProt:P45983 MAPK8
MAPKAPK2
UniProt:P49137 MAPKAPK2
MAP2K5
MEK5
MKK5
PRKMK5
UniProt:Q13163 MAP2K5
BMK1
ERK5
MAPK7
PRKM7
UniProt:Q13164 MAPK7
ORCA
OSIL
SQSTM1
UniProt:Q13501 SQSTM1
ARHGEF1
UniProt:Q92888 ARHGEF1
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
Calcium binds calmodulin
GRB2:SOS binds to SHC-P
SOS mediated nucleotide exchange of RAS (SHC)
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
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
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
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)
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
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