SELECTIVE ACTIVATION OF THE JNK SIGNALING CASCADE AND C-JUN TRANSCRIPTIONAL ACTIVITY BY THE SMALL GTPASES RAC AND CDC42HS
SELECTIVE ACTIVATION OF THE JNK SIGNALING CASCADE AND C-JUN TRANSCRIPTIONAL ACTIVITY BY THE SMALL GTPASES RAC AND CDC42HS
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DOI：
10.1016/s0092-8674(05)80019-4
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发表时间：
1995-06-30
期刊：
影响因子：
64.5
通讯作者：
KARIN, M
中科院分区：
文献类型：
--
作者：
MINDEN, A;LIN, AN;KARIN, M
GTP酶的Rho亚家族参与哺乳动物和酵母中细胞形态的控制。哺乳动物Rac和Cdc 42蛋白分别控制板状伪足和丝状伪足的形成。这些蛋白质还激活调节基因表达的MAP激酶（MAPK）级联。Rac和Cdc 42 H的组成性活化形式是导致JNK和p38/Mpk 2活化的级联的有效活化剂。RhoA没有表现出这种活性，并且没有蛋白质激活MAPK的ERK亚组。JNK，但不是ERK，激活也观察到响应Dbl，癌蛋白，作为一个核苷酸交换因子Cdc 42 Hs。显性干扰等位基因的结果将Rac 1作为Ha-Ras和MEKK之间的中间体，在从生长因子受体和v-Src到JNK激活的信号级联中。JNK和p38激活可能有助于Rac、Cdc 42 Hs和Dbl对细胞生长和增殖的生物学效应。
The Rho subfamily of GTPases is involved in control of cell morphology In mammals and yeast. The mammalian Rac and Cdc42 proteins control formation of lamellipodia and filopodia, respectively. These proteins also activate MAP kinase (MAPK) cascades that regulate gene expression. Constitutively activated forms of Rac and Cdc42Hs are efficient activators of a cascade leading to JNK and p38/Mpk2 activation. RhoA did not exhibit this activity, and none of the proteins activated the ERK subgroup of MAPKs. JNK, but not ERK, activation was also observed in response to Dbl, an oncoprotein that acts as a nucleotide exchange factor for Cdc42Hs. Results with dominant interfering alleles place Rac1 as an intermediate between Ha-Ras and MEKK in the signaling cascade leading from growth factor receptors and v-Src to JNK activation. JNK and p38 activation are likely to contribute to the biological effects of Rac, Cdc42Hs, and Dbl on cell growth and proliferation.