s_mpk1_re25( Survival ):
Grb2 is recruited to the plasma membrane by activated RTKs.
Recruitment to the membrane and tyrosine phosphorylation enhance the enzymatic activity of PLC-g leading to the formation of two second messengers diacylglycerol (DAG) and inositol 145-trisphosphate (IP3). IP3 releases Ca2+ from internal stores which in turn acts in concert with DAG to translocate protein kinase C (PKC) to the cell membrane and stimulate its enzymatic activity.
FGF stimulation leads to phosphorylation of Shp2 on a tyrosine residue that forms a complex with an additional molecule of Grb2. Grb2/Sos complexes are thus recruited directly and indirectly via Shp2 upon tyrosine phosphorylation of FRS2a in response to growth factor stimulation.
PKC may cause phosphorylation of EGFR leading to a decrease in its activity.
PMID:17496910 PMID:15567848 PMID:11447289 PMID:6321473
s_mpk1_re67( Survival ):
Calcium activates the Ras GAP CAPRI (RASA4) that translocates to the PM and downregulates any Ras that is activated on this compartment by the exchange factor SOS.
s_mpk1_re150( Survival ):
Several MAP3Ks upstream of JNK bind RAC1 in a GTP-dependent manner (involving Grb2).
s_mpk1_re9( Survival ):
Sos mediates Ras activation. Interaction of Sos with Ras induces the formation of RasGTP from RasGDP.
Spry is induced by activated ERK through phosphorylation on Tyr55. It positively regulates EGFR signalling by sequestering Cbl whereas it negatively regulates FGFR signalling by sequestering Grb2 from FSR2.
s_mpk1_re273( Survival ):
FGF-induced tyrosine phosphorylation of FRS2 results in complex formation with the adaptor protein Grb2 bound to Cbl by means of its SH3 domains. FGF-induced ternary complex formation among FRS2 Grb2 and Cbl results in ubiquitination and degradation of FRS2 and FGF receptor (FGFR).
PMID:11447289 PMID:11997436 PMID:15173823
s_s_mpk1_re273( Survival ):
Participates in complexes:
In compartment: Plasma Membrane
Participates in reactions:
As Reactant or Product:
- GRB2:RTK*:SOS*@Plasma Membrane + RAC1@Plasma Membrane → GRB2:RAC1|pho:RTK*:SOS*@Plasma Membrane
- GRB2:RAC1|pho:RTK*:SOS*@Plasma Membrane → RAC1@Plasma Membrane + GRB2:RTK*:SOS*@Plasma Membrane
- s_s_mpk1_s1009 + RTK*@Plasma Membrane → GRB2:RTK*:SOS*@Plasma Membrane
- GRB2:RAS*|pho:RTK*:SOS*@Plasma Membrane → RAS*@Plasma Membrane + GRB2:RTK*:SOS*@Plasma Membrane
- RAS*@Plasma Membrane + GRB2:RTK*:SOS*@Plasma Membrane → GRB2:RAS*|pho:RTK*:SOS*@Plasma Membrane