Control of SHB gene expression by protein phosphorylation.

ABSTRACT

To increase our understanding of the role of the Src homology 2 (SH2) domain-containing protein Shb in the mitogenic signal transduction, Shb mRNA contents were determined in the fibroblast-like NIH3T3 cells and the insulin producing beta TC-1 cells under various conditions. In NIH3T3 cells, the serine/ threonine phosphatase inhibitor okadaic acid and the tyrosine kinase inhibitor genistein increased Shb mRNA contents, the protein kinase C activating phorbol ester 12-O-tetradecanoyl 13-acetate (TPA) decreased the Shb mRNA content, whereas the tyrosine kinase inhibitor tyrphostin 25 and the mitogen platelet-derived growth factor (PDGF-BB) had no effect. In beta TC-1 cells, okadaic acid and genistein increased the Shb mRNA content, whereas tyrphostin 25 and serum were without effect. Okadaic acid and genistein decreased the rates of beta TC-1 cell DNA synthesis. It is concluded that expression of the SHB gene is under a complex mode of regulation involving at least three different protein kinases. As a consequence of this, it is likely that SHB gene expression is significantly modulated by conditions of specific activation of certain pathways, whereas its expression appears little influenced by serum and a mitogen.