CRK

Adapter molecule crk ;
Proto-oncogene c-Crk ;
p38 ;

This gene encodes a member of an adapter protein family that binds to several tyrosine-phosphorylated proteins. The product of this gene has several SH2 and SH3 domains (src-homology domains) and is involved in several signaling pathways , recruiting cytoplasmic proteins in the vicinity of tyrosine kinase through SH2-phosphotyrosine interaction. The N-terminal SH2 domain of this protein functions as a positive regulator of transformation whereas the C-terminal SH3 domain functions as a negative regulator of transformation. Two alternative transcripts encoding different isoforms with distinct biological activity have been described. [provided by RefSeq , Jul 2008] ,

Domain:The C-terminal SH3 domain function as a negative modulator for transformation and the N-terminal SH3 domain appears to function as a positive regulator for transformation. ,Domain:The SH2 domain mediates interaction with SHB. ,Function:The Crk-I and Crk-II forms differ in their biological activities. Crk-II has less transforming activity than Crk-I. Crk-II mediates attachment-induced MAPK8 activation , membrane ruffling and cell motility in a Rac-dependent manner. Involved in phagocytosis of apoptotic cells and cell motility via its interaction with DOCK1 and DOCK4. ,PTM:Phosphorylated on Tyr-221 upon cell adhesion. Results in the negative regulation of the association with SH2- and SH3-binding partners , possibly by the formation of an intramolecular interaction of phosphorylated Tyr-221 with the SH2 domain. This leads finally to the down-regulation of the Crk signaling pathway. ,PTM:Phosphorylation of Crk-II (40 kDa) gives rise to a 42 kDa form. ,similarity:Contains 1 SH2 domain. ,similarity:Contains 1 SH3 domain. ,similarity:Contains 2 SH3 domains. ,subcellular location:Translocated to the plasma membrane upon cell adhesion. ,subunit:Interacts with ABL1 , C3G , SOS , MAP4K1 , MAPK8 and DOCK3 via its first SH3 domain. Interacts with BCAR1 , CBL , CBLB , PXN , IRS4 and GAB1 via its SH2 domain upon stimulus-induced tyrosine phosphorylation. Interacts with several tyrosine-phosphorylated growth factor receptors such as EGFR , PDGFR and INSR via its SH2 domain (By similarity) . Interacts with DOCK1 and DOCK4. Interacts with SHB. ,

Cytoplasm . Cell membrane . Translocated to the plasma membrane upon cell adhesion. .