CDC2
CDC28A
CDK1
CDKN1
P34CDC2
UniProt:P06493 CDK1
SRC
SRC1
UniProt:P12931-1 SRC
PLC1
PLCG1
UniProt:P19174 PLCG1
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
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
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
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
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
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