Lysophosphatidic acid stimulates mitogen-activated protein kinase activation via a G-protein-coupled pathway requiring p21ras and p74raf-1.
Lysophosphatidic acid stimulates mitogen-activated protein kinase activation via a G-protein-coupled pathway requiring p21ras and p74raf-1.
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溶血磷脂酸通过需要 p21ras 和 p74raf-1 的 G 蛋白偶联途径刺激丝裂原激活蛋白激酶活化。
DOI：
10.1016/s0021-9258(19)36838-3
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
C. Marshall
中科院分区：
文献类型：
--
作者：
L. R. Howe;C. Marshall
酪氨酸激酶受体的激活通过涉及p21 ras、p74 raf-1（作为MAP激酶）和MAP激酶的途径引起促分裂原活化蛋白（MAP）激酶刺激;然而，异源三聚体G蛋白偶联受体激活MAP激酶的途径尚未确定。由于存在几种MAP激酶激酶，因此已经提出p74 raf-1可能仅将酪氨酸激酶受体偶联至MAP激酶活化。因此，我们研究了G蛋白受体介导的MAP激酶激活对p21 ras和p74 raf-1的需求。溶血磷脂酸通过百日咳毒素敏感途径刺激MAP激酶，该途径被显性负性Ras阻断。溶血磷脂酸刺激的MAP激酶活化通过p74 raf-1的过表达而增强，并通过包含N-末端259个氨基酸的显性负性Raf蛋白的表达而阻断。我们的结论是，溶血磷脂酸激活MAP激酶的G蛋白偶联途径，需要p21 ras和p74 raf-1。
Activation of tyrosine kinase receptors causes mitogen-activated protein (MAP) kinase stimulation via a pathway involving p21ras, p74raf-1 (acting as a MAP kinase kinase kinase), and MAP kinase kinases; however, the pathway by which heterotrimeric G-protein-coupled receptors activate MAP kinases is undefined. Since there are several MAP kinase kinase kinases it has been suggested that p74raf-1 may only couple tyrosine kinase receptors to MAP kinase activation. We therefore investigated the requirement for p21ras and p74raf-1 in G-protein receptor-mediated MAP kinase activation. Lysophosphatidic acid stimulates MAP kinase via a pertussis toxin-sensitive pathway, which is blocked by dominant negative Ras. Lysophosphatidic acid-stimulated MAP kinase activation is potentiated by overexpression of p74raf-1 and blocked by expression of a dominant negative Raf protein comprising the N-terminal 259 amino acids. We conclude that lysophosphatidic acid activates MAP kinases by a G-protein-coupled pathway that requires both p21ras and p74raf-1.