INSERM CJF 93-13 , Hopital Robert Debre , Paris , France .
Cell Signal 8 : 55-8 ( 1996)
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 -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 .