Inhibition of the tyrosine kinase activity of the fibroblast growth factor receptor by the methyltransferase inhibitor 5'-methylthioadenosine.
Stimulation of fibroblasts with basic fibroblast growth factor (bFGF) led to the rapid tyrosine phosphorylation of a number of cellular proteins, including a major substrate of 90 kDa. The methyltransferase inhibitor 5'-methylthioadenosine (MTA) was found to be a specific inhibitor of bFGF-stimulated protein tyrosine phosphorylation in fibroblasts, blocking both receptor autophosphorylation and substrate phosphorylation. MTA had no effect on either epidermal growth factor- or platelet-derived growth factor-stimulated protein tyrosine phosphorylation in fibroblasts. MTA also inhibited both bFGF-stimulated protein tyrosine phosphorylation and neurite outgrowth in PC12 cells. MTA was a specific inhibitor of bFGF-stimulated protein tyrosine phosphorylation only in intact cells. MTA delayed and reduced, but did not inhibit, bFGF internalization and processing. The effects of MTA on bFGF-stimulated tyrosine phosphorylation required only a brief pretreatment with the agent and were readily reversible.
Maher
P A
PA
Department of Molecular and Cellular Growth Biology, Whittier Institute for Diabetes and Endocrinology, La Jolla, California 92037.
D016475:3T3 Cells; D000818:Animals; D003839:Deoxyadenosines / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D008780:Methyltransferases / Q000037:antagonists & inhibitors; D051379:Mice; D008807:Mice, Inbred BALB C; D016716:PC12 Cells; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D017468:Receptors, Fibroblast Growth Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013872:Thionucleosides / Q000494:pharmacology*; D014443:Tyrosine / Q000378:metabolism
D003839:Deoxyadenosines; D017468:Receptors, Fibroblast Growth Factor; D013872:Thionucleosides; D016222:Fibroblast Growth Factor 2; D014443:Tyrosine; C008500:5'-methylthioadenosine; D008780:Methyltransferases; D011505:Protein-Tyrosine Kinases