Identification of major tyrosine-phosphorylated proteins in Csk-deficient cells.
Csk is a non-receptor protein-tyrosine kinase that acts as a negative regulator of Src family tyrosine kinases. Csk-deficient mouse embryos exhibited developmental defects including inability to turn and impaired formation of neural tube. In these embryos, an accumulation of tyrosine phosphorylated proteins was observed as a consequence of constitutive activation of Src family kinases. In order to identify those tyrosine phosphorylated proteins, we established a Csk-deficient cell line from embryos lacking both Csk and the anti-oncogene product p53. On surveying several proteins known as Src substrates, we found that phosphorylation level of p80/85 (cortactin) was markedly elevated in the Csk-deficient cells. Enhancement of cortactin phosphorylation was also seen in Csk-deficient embryos. Furthermore, immunoprecipitated Src was able to directly phosphorylate cortactin in vitro. Thus, we suggest that cortactin is a good substrate of activated Src family kinases in vivo and may play important roles in signaling pathways mediated by Src family kinases.
Nada
S
S
Division of Protein Metabolism, Osaka University, Japan.
Okada
M
M
Aizawa
S
S
Nakagawa
H
H
D000818:Animals; D001665:Binding Sites; D000081247:CSK Tyrosine-Protein Kinase; D002460:Cell Line; D051356:Cortactin; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism*; D019061:src-Family Kinases
D051356:Cortactin; C495869:Cttn protein, mouse; D008840:Microfilament Proteins; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D016392:Proto-Oncogene Proteins pp60(c-src); D019061:src-Family Kinases