Activation of C-terminal Src kinase (Csk) by phosphorylation at serine-364 depends on the Csk-Src homology 3 domain.
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.
Yaqub
Sheraz
S
Department of Medical Biochemistry, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1112, Blindern, N-0317 Oslo, Norway.
Abrahamsen
Hilde
H
Zimmerman
Bastian
B
Kholod
Natalya
N
Torgersen
Knut Martin
KM
Mustelin
Tomas
T
Herberg
Friedrich W
FW
Taskén
Kjetil
K
Vang
Torkel
T
D000081247:CSK Tyrosine-Protein Kinase; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004789:Enzyme Activation / Q000502:physiology; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D012694:Serine / Q000378:metabolism*; D019061:src-Family Kinases
D012694:Serine; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; D017868:Cyclic AMP-Dependent Protein Kinases