Goldschmidt-Clermont P J, Kim J W, Machesky L M, Rhee S G, Pollard T D
Department of Cell Biology and Anatomy, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Science. 1991 Mar 8;251(4998):1231-3. doi: 10.1126/science.1848725.
Epidermal growth factor and platelet-derived growth factor can stimulate the production of the second messenger inositol trisphosphate in responsive cells, but the biochemical pathway for these signaling events has been uncertain because the reactions have not been reconstituted with purified molecules in vitro. A reconstitution is described that requires not only the growth factor, its receptor with tyrosine kinase activity, and the soluble phospholipase C-gamma 1, but also the small soluble actin-binding protein profilin. Profilin binds to the substrate phosphatidylinositol 4,5-bisphosphate and inhibits its hydrolysis by unphosphorylated phospholipase C-gamma 1. Phosphorylation of phospholipase C-gamma 1 by the epidermal growth factor receptor tyrosine kinase overcomes the inhibitory effect of profilin and results in an effective activation of phospholipase C-gamma 1.
表皮生长因子和血小板衍生生长因子可刺激反应性细胞中第二信使三磷酸肌醇的产生，但这些信号事件的生化途径一直不确定，因为这些反应尚未在体外使用纯化分子进行重构。本文描述了一种重构方法，该方法不仅需要生长因子、具有酪氨酸激酶活性的其受体以及可溶性磷脂酶C-γ1，还需要小的可溶性肌动蛋白结合蛋白丝切蛋白。丝切蛋白与底物磷脂酰肌醇4,5-二磷酸结合，并抑制其被未磷酸化的磷脂酶C-γ1水解。表皮生长因子受体酪氨酸激酶对磷脂酶C-γ1的磷酸化克服了丝切蛋白的抑制作用，并导致磷脂酶C-γ1的有效激活。
