ACTIVATION OF MITOGEN-ACTIVATED PROTEIN-KINASE KINASE BY V-RAF IN NIH 3T3 CELLS AND INVITRO
ACTIVATION OF MITOGEN-ACTIVATED PROTEIN-KINASE KINASE BY V-RAF IN NIH 3T3 CELLS AND INVITRO
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DOI：
10.1126/science.1326789
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发表时间：
1992-09-04
期刊：
影响因子：
56.9
通讯作者：
STURGILL, TW
中科院分区：
文献类型：
--
作者：
DENT, P;HASER, W;STURGILL, TW
丝裂原激活蛋白 (MAP) 激酶是 42-和 44-kD 丝氨酸-苏氨酸蛋白激酶，在用丝裂原和生长因子刺激的细胞中通过酪氨酸和苏氨酸磷酸化来激活。 MAP 激酶和激活它的蛋白激酶（MAP 激酶激酶）在被含有两种致癌形式（p35EC12、p37(22W)）c-Raf-1 蛋白激酶的病毒感染的 NIH 3T3 细胞中被组成型激活。从感染ECl 2 或22W病毒的细胞中纯化的v-Raf蛋白在体外激活骨骼肌中的MAP激酶激酶。此外，细菌表达的 v-Raf 融合蛋白（谷胱甘肽 S-转移酶-p37(22W)）也在体外激活 MAP 激酶。这些发现表明 c-Raf-1 在促有丝分裂信号传导中的一项功能是磷酸化和激活 MAP 激酶激酶。
Mitogen-activated protein (MAP) kinases are 42- and 44-kD serine-threonine protein kinases that are activated by tyrosine and threonine phosphorylation in cells stimulated with mitogens and growth factors. MAP kinase and the protein kinase that activates it (MAP kinase kinase) were constitutively activated in NIH 3T3 cells infected with viruses containing either of two oncogenic forms (p35EC12, p37(22W)) of the c-Raf-1 protein kinase. The v-Raf proteins purified from cells infected with ECl 2 or 22W viruses activated MAP kinase kinase from skeletal muscle in vitro. Furthermore, a bacterially expressed v-Raf fusion protein (glutathione S-transferase-p37(22W)) also activated MAP kinase kinase in vitro. These findings suggest that one function of c-Raf-1 in mitogenic signaling is to phosphorylate and activate MAP kinase kinase.