Mitotic activation of c-Src is suppressed by Csk.
The kinase activity of the proto-oncogene product, c-Src, increases during mitosis through partial dephosphorylation of Tyr527, the negative regulatory site of c-Src. To examine whether or not Csk, a candidate kinase specific for Tyr527, is involved in this regulation, we developed a Balb/c 3T3 cell line overexpressing Csk and a Csk-deficient cell line. The overexpression of wild-type Csk caused significant suppression of the c-Src activity during mitosis. A membrane-targeted Csk, which has an amino-terminal myristylation signal of c-Src, exhibited an effective suppression of the c-Src activity, even though its expression level was lower than that of endogenous Csk. Concomitant with the suppression of the c-Src activation, the level of tyrosine phosphorylation of a cortactin-related protein, a potential substrate of c-Src in vivo, was reduced. In contrast, the Csk-deficient cells exhibited constitutive activation of c-Src, which showed no significant change in its activity during mitosis. These results suggest that Csk indeed participates in the regulation of the c-Src activity during mitosis.
Ohsato
Y
Y
Division of Protein Metabolism, Osaka University.
Nada
S
S
Okada
M
M
Nakagawa
H
H
D016475:3T3 Cells; D000818:Animals; D000081247:CSK Tyrosine-Protein Kinase; D005786:Gene Expression Regulation; D051379:Mice; D008807:Mice, Inbred BALB C; D008938:Mitosis; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000494:pharmacology*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured; D019061:src-Family Kinases
D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D016392:Proto-Oncogene Proteins pp60(c-src); D019061:src-Family Kinases