Nishibe S, Wahl M I, Hernández-Sotomayor S M, Tonks N K, Rhee S G, Carpenter G
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232-0146.
Science. 1990 Nov 30;250(4985):1253-6. doi: 10.1126/science.1700866.
Phospholipase C-gamma 1 (PLC-gamma 1), an isozyme of the phosphoinositide-specific phospholipase C family, which occupies a central role in hormonal signal transduction pathways, is an excellent substrate for the epidermal growth factor (EGF) receptor tyrosine kinase. Epidermal growth factor elicits tyrosine phosphorylation of PLC-gamma 1 and phosphatidylinositol 4,5-bisphosphate hydrolysis in various cell lines. The ability of tyrosine phosphorylation to activate the catalytic activity of PLC-gamma 1 was tested. Tyrosine phosphorylation in intact cells or in vitro increased the catalytic activity of PLC-gamma 1. Also, treatment of EGF-activated PLC-gamma 1 with a tyrosine-specific phosphatase substantially decreased the catalytic activity of PLC-gamma 1. These results suggest that the EGF-stimulated formation of inositol 1,4,5-trisphosphate and diacylglycerol in intact cells results, at least in part, from catalytic activation of PLC-gamma 1 through tyrosine phosphorylation.
磷脂酶C-γ1（PLC-γ1）是磷酸肌醇特异性磷脂酶C家族的一种同工酶，在激素信号转导途径中起核心作用，是表皮生长因子（EGF）受体酪氨酸激酶的优良底物。表皮生长因子可引发PLC-γ1的酪氨酸磷酸化以及多种细胞系中磷脂酰肌醇4,5-二磷酸的水解。对酪氨酸磷酸化激活PLC-γ1催化活性的能力进行了测试。完整细胞内或体外的酪氨酸磷酸化均增强了PLC-γ1的催化活性。此外，用酪氨酸特异性磷酸酶处理EGF激活的PLC-γ1可显著降低其催化活性。这些结果表明，完整细胞中EGF刺激产生的肌醇1,4,5-三磷酸和二酰基甘油，至少部分是通过酪氨酸磷酸化对PLC-γ1的催化激活所致。
