Vara Prasad M V, Shore S K, Dhanasekaran N
Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA 19140.
Oncogene. 1994 Aug;9(8):2425-9.
Expression of the constitutively activated mutant alpha-subunit of the heterotrimeric G protein G alpha 13 (alpha 13Q226L) leads to the transformation of NIH-3T3 cells. An analysis of the mitogenic pathway mediated by alpha 13Q226L indicated that the expression of the primary response genes, early growth response gene-1 (Egr-1, a nuclear transcription factor with zinc-finger motif) and c-fos (a leucine zipper transcription factor as well as a protooncogene) are constitutively activated in alpha 13Q226L-transformants. While ras-transformed cells did not express Egr-1, cells transformed by the GTPase deficient mutant alpha-subunit of G alpha 12 (alpha 12Q229L) exhibited a "weak" expression, suggesting that the induction of Egr-1 and c-fos is intrinsic to G alpha 13 signaling pathway and not a consequence of the transformed phenotype. Taken together, these results provide the first evidence that the G alpha 13 signaling pathway involves the activation of specific transcription factors and defines the expression of these nuclear transcription factors as a possible molecular mechanism in alpha 13Q226L-mediated cell proliferation and transformation.
异三聚体G蛋白Gα13的组成型激活突变体α亚基（α13Q226L）的表达导致NIH-3T3细胞发生转化。对由α13Q226L介导的促有丝分裂途径的分析表明，初级反应基因早期生长反应基因-1（Egr-1，一种具有锌指基序的核转录因子）和c-fos（一种亮氨酸拉链转录因子以及原癌基因）在α13Q226L转化细胞中被组成型激活。虽然ras转化细胞不表达Egr-1，但由Gα12的GTP酶缺陷突变体α亚基（α12Q229L）转化的细胞表现出“微弱”表达，这表明Egr-1和c-fos的诱导是Gα13信号通路所固有的，而不是转化表型的结果。综上所述，这些结果提供了首个证据，即Gα13信号通路涉及特定转录因子的激活，并将这些核转录因子的表达定义为α13Q226L介导的细胞增殖和转化中可能的分子机制。
