Minden A, Lin A, Claret F X, Abo A, Karin M
Department of Pharmacology, University of California, San Diego School of Medicine, La Jolla 92093-0636, USA.
Cell. 1995 Jun 30;81(7):1147-57. doi: 10.1016/s0092-8674(05)80019-4.
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.
GTP酶的Rho亚家族参与调控哺乳动物和酵母中的细胞形态。哺乳动物的Rac和Cdc42蛋白分别控制片状伪足和丝状伪足的形成。这些蛋白还激活调节基因表达的丝裂原活化蛋白激酶（MAPK）级联反应。组成型激活形式的Rac和Cdc42Hs是导致JNK和p38/Mpk2激活的级联反应的有效激活剂。RhoA不表现出这种活性，并且这些蛋白均未激活MAPK的ERK亚组。响应Dbl（一种作为Cdc42Hs核苷酸交换因子的癌蛋白）也观察到JNK而非ERK的激活。显性干扰等位基因的结果表明，在从生长因子受体和v-Src到JNK激活的信号级联反应中，Rac1是Ha-Ras和MEKK之间的中间体。JNK和p38的激活可能有助于Rac、Cdc42Hs和Dbl对细胞生长和增殖的生物学效应。
