SRC Rabbit Polyclonal Antibody

Function

Src (pronounced "sarc" as it is short for sarcoma) is a proto-oncogene encoding a tyrosine kinase. It belongs to a family of non-receptor tyrosine kinases called Src family kinases. c-Src is made up of 6 functional regions: Src homology (SH) 4 domain (SH4 domain), unique region, SH3 domain, SH2 domain, catalytic domain and short regulatory tail. When Src is inactive, the phosphorylated tyrosine group at the 527 position interacts with the SH2 domain which helps the SH3 domain interact with the linker domain and consequently keeps the inactive unit tightly bound. The activation of c-Src causes the dephosphorylation of the tyrosine 527 which causes the structure to be destabilized and then result in the opening up of the SH3, SH2 and the kinase domains and autophosphorylation of tyrosine 416. The activation of the c-Src pathway has been observed in about 50% of tumors from colon, liver, lung, breast and the pancreas.

Background References

1. "beta-arrestin1 interacts with the catalytic domain of the tyrosine kinase c-SRC. Role of beta-arrestin1-dependent targeting of c-SRC in receptor endocytosis." Miller W.E., Maudsley S., Ahn S., Khan K.D., Luttrell L.M., Lefkowitz R.J. J. Biol. Chem. 275:11312-11319(2000)

2. "Development and characterization of potent and specific peptide inhibitors of p60c-src protein tyrosine kinase using pseudosubstrate-based inhibitor design approach." Kamath J.R., Liu R., Enstrom A.M., Lou Q., Lam K.S. J. Pept. Res. 62:260-268(2003)

3. "The tyrosine kinase c-Src enhances RIG-I (retinoic acid-inducible gene I)-elicited antiviral signaling." Johnsen I.B., Nguyen T.T., Bergstroem B., Fitzgerald K.A., Anthonsen M.W. J. Biol. Chem. 284:19122-19131(2009)

Sequence Similarity

Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily.

Tissue Specificity

Expressed ubiquitously. Platelets, neurons and osteoclasts express 5-fold to 200-fold higher levels than most other tissues.

Post-translational Modification

Myristoylated at Gly-2, and this is essential for targeting to membranes.; Dephosphorylated at Tyr-530 by PTPRJ (By similarity). Phosphorylated on Tyr-530 by c-Src kinase (CSK). The phosphorylated form is termed pp60c-src. Dephosphorylated by PTPRJ at Tyr-419. Normally maintained in an inactive conformation with the SH2 domain engaged with Tyr-530, the SH3 domain engaged with the SH2-kinase linker, and Tyr-419 dephosphorylated. Dephosphorylation of Tyr-530 as a result of protein tyrosine phosphatase (PTP) action disrupts the intramolecular interaction between the SH2 domain and Tyr-530, Tyr-419 can then become autophosphorylated, resulting in SRC activation. Phosphorylation of Tyr-530 by CSK allows this interaction to reform, resulting in SRC inactivation. CDK5-mediated phosphorylation at Ser-75 targets SRC to ubiquitin-dependent degradation and thus leads to cytoskeletal reorganization. Phosphorylated by PTK2/FAK1; this enhances kinase activity. Phosphorylated by PTK2B/PYK2; this enhances kinase activity.; S-nitrosylation is important for activation of its kinase activity.; Ubiquitinated in response to CDK5-mediated phosphorylation. Ubiquitination mediated by CBLC requires SRC autophosphorylation at Tyr-419 and may lead to lysosomal degradation.

Subcellular Location

Cell membrane, nucleus, cytoplasm

UNIPROT

SwissProt: P12931 Human

SwissProt: P05480 Mouse

SwissProt: Q9WUD9 Rat

Synonyms