Yaqub Sheraz, Abrahamsen Hilde, Zimmerman Bastian, Kholod Natalya, Torgersen Knut Martin, Mustelin Tomas, Herberg Friedrich W, Taskén Kjetil, Vang Torkel
Department of Medical Biochemistry, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1112, Blindern, N-0317 Oslo, Norway.
Biochem J. 2003 May 15;372(Pt 1):271-8. doi: 10.1042/BJ20030021.
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 Ser(364) 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.
在本研究中,我们探究了蛋白激酶A(PKA)介导的C端Src激酶(Csk)激活机制。尽管分离的Csk激酶结构域被PKA磷酸化至Ser(364),其化学计量与野生型Csk相同,但仅在存在纯化的Src同源3结构域(SH3结构域)时,才观察到PKA对分离的Csk激酶结构域有显著激活作用。此外,通过表面等离子体共振评估,PKA介导的激酶结构域磷酸化促进了SH3与激酶结构域之间的相互作用。这表明激酶结构域与SH3结构域之间的整体结构域组织和相互作用对于Csk的活性及其受PKA的调节很重要。