血小板衍生生长因子对丝裂原活化蛋白激酶的激活取决于磷脂酰胆碱特异性磷脂酶C、蛋白激酶C-ζ和Raf-1的顺序激活。
Platelet-derived growth factor activation of mitogen-activated protein kinase depends on the sequential activation of phosphatidylcholine-specific phospholipase C, protein kinase C-zeta and Raf-1.
作者信息
van Dijk M C, Hilkmann H, van Blitterswijk W J
机构信息
Division of Cellular Biochemistry, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
出版信息
Biochem J. 1997 Jul 15;325 ( Pt 2)(Pt 2):303-7. doi: 10.1042/bj3250303.
Abstract
The mechanism of Raf-1 activation by platelet-derived growth factor (PDGF) is poorly defined. We previously reported that, in Rat-1 fibroblasts, PDGF activates a phosphatidylcholine-specific phospholipase C (PC-PLC) and that the product, diacylglycerol, somehow activates protein kinase C-zeta (PKC-zeta). Both PC-PLC and PKC-zeta activities were required for PDGF activation of mitogen-activated protein kinase (MAPK). Now we report that MAPK activation by exogenous PC-PLC depends on Raf-1 activation. PKC-zeta co-immunoprecipitates with, phoshorylates and activates Raf-1, suggesting that in the PDGF- and PC-PLC-activated MAPK pathway, PKC-zeta operates in a signalling complex as a direct activator of Raf-1.
摘要
血小板衍生生长因子（PDGF）激活Raf-1的机制尚不清楚。我们之前报道过，在大鼠1型成纤维细胞中，PDGF激活磷脂酰胆碱特异性磷脂酶C（PC-PLC），其产物二酰基甘油以某种方式激活蛋白激酶C-ζ（PKC-ζ）。有丝分裂原激活蛋白激酶（MAPK）的PDGF激活需要PC-PLC和PKC-ζ的活性。现在我们报道，外源性PC-PLC激活MAPK依赖于Raf-1的激活。PKC-ζ与Raf-1共免疫沉淀、磷酸化并激活Raf-1，这表明在PDGF和PC-PLC激活的MAPK途径中，PKC-ζ作为Raf-1的直接激活剂在信号复合物中发挥作用。
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Diacylglycerol generated by exogenous phospholipase C activates the mitogen-activated protein kinase pathway independent of Ras- and phorbol ester-sensitive protein kinase C: dependence on protein kinase C-zeta.外源性磷脂酶C产生的二酰甘油激活丝裂原活化蛋白激酶途径，该途径独立于Ras和佛波酯敏感的蛋白激酶C：依赖于蛋白激酶C-ζ 。
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