Restriction of Src activity by Cullin-5.

ABSTRACT: Src is a nonreceptor tyrosine kinase that coordinates responses to diverse soluble and adhesive signaling molecules and regulates cell proliferation, survival, differentiation and migration. Normally, Src activity is tightly regulated, and Src-catalyzed phosphorylation is counterbalanced by phosphotyrosine phosphatases. However, deregulated mutant Src causes malignant transformation when highly expressed. Src transformation is dose dependent, but it has been unclear how much mutant Src, compared with endogenous Src, is required for transformation. Here, we show that transformation requires high-level overexpression of mutant src mRNA, in part because active Src protein is degraded by ubiquitin-mediated proteolysis. We show that active but not inactive Src protein is downregulated depending

SUBMITTER: Laszlo GS 

PROVIDER: S-EPMC2730496 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature