Control of SHB gene expression by protein phosphorylation.
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.
Lavergne
C
C
INSERM CJF 93-13, Hopital Robert Debré, Paris, France.
Mares
J
J
Karlsson
T
T
Bréant
B
B
Welsh
M
M
D016475:3T3 Cells / Q000187:drug effects; D000818:Animals; D000077214:Becaplermin; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004988:Ethers, Cyclic / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000502:physiology*; D019833:Genistein; D007529:Isoflavones / Q000494:pharmacology; D051379:Mice; D009570:Nitriles / Q000494:pharmacology; D019319:Okadaic Acid; D010766:Phosphorylation / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011499:Protein Processing, Post-Translational; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D020032:Tyrphostins
D004791:Enzyme Inhibitors; D004988:Ethers, Cyclic; D007529:Isoflavones; D009570:Nitriles; D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; C085634:Shb protein, mouse; D020032:Tyrphostins; C079836:tyrphostin 25; D000077214:Becaplermin; D019319:Okadaic Acid; D019833:Genistein; D013755:Tetradecanoylphorbol Acetate