Src tyrosine kinase activation

In the restrained state, the SH2 domain forms a salt bridge with phosphotyrosine , and the SH3 domain binds to the kinase domain via a polyproline type II left-handed helix. The SH2 and SH3 domains occur on the backside of the kinase domain away from the active site where they stabilize a dormant enzyme conformation.

Protein-tyrosine phosphatases such as PTPalpha displace phosphotyrosine from the Src SH2 domain and mediate its dephosphorylation leading to Src kinase activation. Figure 3. Results Cooperative activation by SH3 and SH3 ligands To test for cooperativity, we expressed and purified the down-regulated form of the Src kinase Hck.

Figure 1. Figure 2. Activated Src in focal adhesions Integrin signaling leads to activation of Src and Src-Cas interactions at focal adhesions [ 34 — 37 ]. Discussion Our results provide support to the hypothesis that the SH3 and SH2 domains of Src family kinases act in a cooperative manner to repress the kinases. Acknowledgments We thank Chris Gordon for assistance with microscopy, and Xiaoling Wang for preliminary kinetic experiments.

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