Kortenjann M, Shaw P E
Max-Planck-Institut für Immunobiologie, Spemann Laboratories, Freiburg, Germany.
Oncogene. 1995 Nov 16;11(10):2105-12.
The MAP kinase pathway impinging on ERK2 has been shown to be integrally associated with mitogenic signalling in many cell types. Previously, we and others have demonstrated that oncogenic forms of Raf-1 kinase, when expressed in fibroblasts, lead to the constitutive activation of ERK2, the de-regulation of c-fos expression and increased cell proliferation. Here we describe an exception to this scenario. In Rat6 cells, although both ERK1 and ERK2 are activated in response to mitogens that induce c-fos expression, such as Epidermal Growth Factor (EGF), lysophosphatidic acid (LPA) or serum, expression of v-Raf fails to induce c-fos expression and increase proliferation. However, ERK2 is activated by v-Raf expression. The co-transfection of an interfering mutant of ERK2 has no effect on the level of c-fos reporter expression in Rat6 cells whereas the analogous ERK1 mutant reduces its expression. Furthermore, the spontaneous focus formation observed in Rat6 cells is susceptible to the interfering mutant of ERK1 but resistant to that of ERK2. Thus, not only do mitogenic signals appear to by-pass both Raf-1 kinase and ERK2, the Raf-1-ERK2 pathway seems to be functionally compromised in Rat6 cells as its activation leads neither to c-fos expression nor to increased proliferation.
已证明作用于ERK2的丝裂原活化蛋白激酶（MAP）途径在许多细胞类型中与促有丝分裂信号传导密切相关。此前，我们和其他人已证明，致癌形式的Raf-1激酶在成纤维细胞中表达时，会导致ERK2的组成型激活、c-fos表达失调以及细胞增殖增加。在此，我们描述了这种情况的一个例外。在Rat6细胞中，尽管ERK1和ERK2都会因诱导c-fos表达的促有丝分裂原（如表皮生长因子（EGF）、溶血磷脂酸（LPA）或血清）而被激活，但v-Raf的表达未能诱导c-fos表达和增加增殖。然而，ERK2会因v-Raf的表达而被激活。ERK2的干扰突变体共转染对Rat6细胞中c-fos报告基因的表达水平没有影响，而类似的ERK1突变体则会降低其表达。此外，在Rat6细胞中观察到的自发灶形成对ERK1的干扰突变体敏感，但对ERK2的干扰突变体有抗性。因此，不仅促有丝分裂信号似乎绕过了Raf-1激酶和ERK2，Raf-1-ERK2途径在Rat6细胞中的功能似乎也受到损害，因为其激活既不会导致c-fos表达，也不会导致增殖增加。
