Honda Z, Takano T, Gotoh Y, Nishida E, Ito K, Shimizu T
Department of Biochemistry, Faculty of Medicine, University of Tokyo, Japan.
J Biol Chem. 1994 Jan 21;269(3):2307-15.
The platelet-activating factor (PAF) was seen to potently activate mitogen-activated protein (MAP) kinase and MAP kinase kinase through the cloned guinea pig PAF receptor stably expressed in Chinese hamster ovary (CHO) cells. Both 42- and 44-kDa MAP kinases were activated and tyrosine-phosphorylated in response to PAF. The PAF receptor also triggered the production of inositol phosphates and the release of arachidonic acid and inhibited cyclic AMP accumulation. Differential inhibitory effects of pertussis toxin (PTX) on these signals suggested that the PAF receptor couples to both PTX-sensitive and -insensitive G proteins in CHO cells. MAP kinase and MAP kinase activations were partially regulated by PTX-sensitive G proteins. The PAF receptor did not trigger any detectable increase in the GTP form of Ras under the conditions in which the human insulin receptor expressed in the same parent CHO cells potently increased the level. Since these agonists induced comparable MAP kinase activations through cognate receptors, Ras seems to play different roles in MAP kinase activation by the two different classes of receptors. The activation of MAP kinase by the cloned PAF receptor may explain part of the mechanisms underlying PAF-induced differentiation and proliferation in non-inflammatory cells.
通过在中国仓鼠卵巢（CHO）细胞中稳定表达的克隆豚鼠血小板活化因子（PAF）受体，可观察到PAF能有效激活丝裂原活化蛋白（MAP）激酶和MAP激酶激酶。42 kDa和44 kDa的MAP激酶均被激活并发生酪氨酸磷酸化以响应PAF。PAF受体还引发肌醇磷酸的产生、花生四烯酸的释放，并抑制环磷酸腺苷（cAMP）的积累。百日咳毒素（PTX）对这些信号的不同抑制作用表明，PAF受体在CHO细胞中与对PTX敏感和不敏感的G蛋白偶联。MAP激酶和MAP激酶的激活部分受PTX敏感G蛋白的调节。在相同亲本CHO细胞中表达的人胰岛素受体能有效提高Ras的GTP形式水平的条件下，PAF受体未引发Ras的任何可检测到的增加。由于这些激动剂通过同源受体诱导了相当的MAP激酶激活，Ras似乎在两类不同受体激活MAP激酶过程中发挥不同作用。克隆的PAF受体激活MAP激酶可能解释了PAF诱导非炎症细胞分化和增殖的部分潜在机制。
