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