proto-oncogene C-crk; p38; adapter molecule crk (CRK)
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Introduction
Function:
- adaptor protein in signal transduction through ras analogous to grb2
- specificity of crk SH2-domain differs from that of grb2, resulting in a different spectrum of signal transduction activities
- Crk associates with 2 different GNDS
- Crk may bind phosphorylated Tyr-527 of c-src
- Crk binds to paxillin through its SH2 domain & to proline-rich regions of C3G, mSos1 & abl through its SH3 domains
- binding to C3G is through its C-terminal SH3 domain[6]
- the Crk-I & Crk-II isoforms differ in their biological activities
- Crk-II has less transforming activity than Crk-I
- Crk-II mediates attachment-induced MAPK8 activation, membrane ruffling & cell motility (Rac-dependent)
- role in phagocytosis of apoptotic cells & cell motility via its interaction with DOCK1 & DOCK4
- phosphorylation of Crk-II (40 kD) gives rise to a 42 kD form
- phosphorylation of Tyr-221 upon cell adhesion results in negative regulation of association with SH2- & SH3-binding partners, possibly via intramolecular interaction of phosphorylated Tyr-221 with the SH2 domain leading to down-regulation of the Crk signaling pathway
- interacts with ABL1, C3G, SOS, MAP4K1, MAPK8 & DOCK3 via its first SH3 domain
- interacts with BCAR1, CBL, CBLB, PXN, IRS4 & GAB1 via its SH2 domain upon stimulus-induced Tyr phosphorylation
- interacts with several Tyr-phosphorylated growth factor receptors including: EGFR, PDGFR & INSR via its SH2 domain (putative)
- interacts with DOCK1 & DOCK4
- interacts with SHB
Structure
- C-terminal SH3 domain negatively modulates transformation
- N-terminal SH3 domain appears to positively regulate transformation
- SH2 domain mediates interaction with SHB
- contains 1 SH2 domain
- contains 2 SH3 domains
Compartment
- cytoplasm (putative), cell membrane
- translocated to the plasma membrane upon cell adhesion (putative)
Alternative splicing
named isoforms=2; Crk-I & Crk-II
Notes
- pronounced 'crack'
More general terms
References
- ↑ Matsuda M, Mayer BJ, Fukui Y, Hanafusa H. Binding of transforming protein, P47gag-crk, to a broad range of phosphotyrosine-containing proteins. Science. 1990 Jun 22;248(4962):1537-9. PMID: https://www.ncbi.nlm.nih.gov/pubmed/1694307
- ↑ Anderson D, Koch CA, Grey L, Ellis C, Moran MF, Pawson T. Binding of SH2 domains of phospholipase C gamma 1, GAP, and Src to activated growth factor receptors. Science. 1990 Nov 16;250(4983):979-82. PMID: https://www.ncbi.nlm.nih.gov/pubmed/2173144
- ↑ Molecular Cell Biology (2nd ed) Darnell J; Lodish H & Baltimore D (eds), Scientific American Books, WH Freeman, NY 1990, pg 989
- ↑ Cantley LC, Auger KR, Carpenter C, Duckworth B, Graziani A, Kapeller R, Soltoff S. Oncogenes and signal transduction. Cell. 1991 Jan 25;64(2):281-302. Review. Erratum in: Cell 1991 May 31;65(5):following 914. PMID: https://www.ncbi.nlm.nih.gov/pubmed/1846320
- ↑ Pawson T. Protein modules and signalling networks. Nature. 1995 Feb 16;373(6515):573-80. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/7531822
- ↑ 6.0 6.1 Clark EA & Brugge JS Integrins and signal transduction pathways: the road taken. Science 268:233 1995 PMID: https://www.ncbi.nlm.nih.gov/pubmed/7716514
- ↑ UniProt http://www.uniprot.org/uniprot/P46108.html