Molecular cloning of mitogen-activated protein ERK kinase kinases (MEKK) 2 and 3 - Regulation of sequential phosphorylation pathways involving mitogen-activated protein kinase and c-Jun kinase
Molecular cloning of mitogen-activated protein ERK kinase kinases (MEKK) 2 and 3 - Regulation of sequential phosphorylation pathways involving mitogen-activated protein kinase and c-Jun kinase
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DOI：
10.1074/jbc.271.10.5361
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发表时间：
1996-03-08
影响因子：
4.8
通讯作者：
Johnson, GL
中科院分区：
文献类型：
--
作者：
Blank, JL;Gerwins, P;Johnson, GL
丝裂原活化蛋白/ERK激酶(MEKK)磷酸化并激活蛋白激酶，进而磷酸化并激活p42/44丝裂原活化蛋白激酶(MAPK)、c-jun/应激激活蛋白激酶(JNKs)和p38/Hog1激酶。我们已经分离了两个新的哺乳动物MEKK(Mekk2和Mekk3)的cDNA，Mekk2和Mekk3分别编码69.7和71 kDa的蛋白质。编码在Coop-末端部分的激酶结构域有94%的保守性，而NH2-末端部分的同源性约为65%，这表明该区域可能编码了对这两种激酶进行差异调控的序列。在HEK293细胞中表达Mekk2或3可激活p42/44(MAPK)和JNK，但不能激活p38/Hog1激酶。免疫沉淀的Mekk2使MAP激酶、MEK1和JNK激酶磷酸化。Mekk2和Mekk3的表达滴定结果表明，Mek2优先激活JNK，而Mekk3优先激活p42/44(MAPK)。这些发现定义了一个Mekk蛋白家族，能够调节涉及MAPK成员的顺序蛋白激酶途径。
Mitogen-activated protein/ERK kinase kinases (MEKKs) phosphorylate and activate protein kinases which in turn phosphorylate and activate the p42/44 mitogen-activated protein kinase (MAPK), c-Jun/stress-activated protein kinases (JNKs), and p38/Hog1 kinase. We have isolated the cDNAs for two novel mammalian MEKKs (MEKK 2 and 3), MEKK 2 and 3 encode proteins of 69.7 and 71 kDa, respectively. The kinase domains encoded in the COOP-terminal moiety are 94% conserved; the NH2-terminal moieties are approximately 65% homologous, suggesting this region may encode sequences conferring differential regulation of the two kinases. Expression of MEKK 2 or 3 in HEK293 cells results in activation of p42/44(MAPK) and JNK but not of p38/Hog1 kinase. Immunoprecipitated MEKK 2 phosphorylated the MAP kinase kinases, MEK 1, and JNK kinase. Titration of MEKK 2 and 3 expression in transfection assays indicated that MEEK 2 preferentially activated JNK while MEKK 3 preferentially activated p42/44(MAPK). These findings define a family of MEKK proteins capable of regulating sequential protein kinase pathways involving MAPK members.