In the present study, we investigate the mechanism for the protein kinase A (PKA)-mediated activation of C-terminal Src kinase (Csk). Although isolated Csk kinase domain was phosphorylated at Ser364 by PKA to the same stoichiometry as wild-type Csk, significant activation of the isolated Csk kinase domain by PKA was observed only in the presence of the purified Src homology 3 domain (SH3 domain). Furthermore, the interaction between the SH3 and kinase domains was facilitated by PKA-mediated phosphorylation of the kinase domain, as evaluated by surface plasmon resonance. This suggests that an overall structural domain organization and interaction between the kinase and SH3 domains are important for the activity of Csk and its regulation by PKA.

Abbreviations used: Csk, C-terminal Src kinase; Cbp, Csk-binding protein; GST, glutathione S-transferase; PAG, phosphoprotein associated with glycosphingolipid-enriched microdomains; PKA, protein kinase A; RU, response unit; SFK, Src family kinase; SH domain, Src homology domain; SPR, surface plasmon resonance.

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Author notes


Present address: Department of Biological Chemistry, University of Michigan, U.S.A.