Maher P A
Department of Molecular and Cellular Growth Biology, Whittier Institute for Diabetes and Endocrinology, La Jolla, California 92037.
J Biol Chem. 1993 Feb 25;268(6):4244-9.
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.
用碱性成纤维细胞生长因子（bFGF）刺激成纤维细胞会导致许多细胞蛋白迅速发生酪氨酸磷酸化，包括一种90 kDa的主要底物。发现甲基转移酶抑制剂5'-甲硫腺苷（MTA）是成纤维细胞中bFGF刺激的蛋白酪氨酸磷酸化的特异性抑制剂，可阻断受体自身磷酸化和底物磷酸化。MTA对成纤维细胞中表皮生长因子或血小板衍生生长因子刺激的蛋白酪氨酸磷酸化均无影响。MTA还抑制PC12细胞中bFGF刺激的蛋白酪氨酸磷酸化和神经突生长。MTA仅在完整细胞中是bFGF刺激的蛋白酪氨酸磷酸化的特异性抑制剂。MTA延迟并减少了，但并未抑制bFGF的内化和加工。MTA对bFGF刺激的酪氨酸磷酸化的作用仅需用该试剂进行短暂预处理，且易于逆转。
