Format

Send to

Choose Destination
Oncogene. 2004 Oct 18;23(48):7918-27.

Structure and regulation of Src family kinases.

Author information

1
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Dana-Farber Cancer Institute, 44 Binney St., Boston, MA 02115, USA.

Abstract

Src family kinases are prototypical modular signaling proteins. Their conserved domain organization includes a myristoylated N-terminal segment followed by SH3, SH2, and tyrosine kinase domains, and a short C-terminal tail. Structural dissection of Src kinases has elucidated the canonical mechanisms of phosphotyrosine recognition by the SH2 domain and proline-motif recognition by the SH3 domain. Crystallographic analysis of nearly intact Src kinases in the autoinhibited state has shown that these protein interaction motifs turn inward and lock the kinase in an inactive conformation via intramolecular interactions. The autoinhibited Src kinase structures reveal a mode of domain assembly used by other tyrosine kinases outside the Src family, including Abl and likely Tec family kinases. Furthermore, they illustrate the underlying regulatory principles that have proven to be general among diverse modular signaling proteins. Although there is considerable structural information available for the autoinhibited conformation of Src kinases, how they may assemble into active signaling complexes with substrates and regulators remains largely unexplored.

PMID:
15489910
DOI:
10.1038/sj.onc.1208081
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center