Olson M F, Sterpetti P, Nagata K, Toksoz D, Hall A
Department of Biochemistry, University College London, UK.
Oncogene. 1997 Dec 4;15(23):2827-31. doi: 10.1038/sj.onc.1201594.
Members of the Dbl-homology (DH) family of proteins promote guanine nucleotide exchange on Rho GTPases. Lbc, which specifically acts on Rho but not Rac or Cdc42, was isolated as a transforming oncogene and is composed of a DH and a Pleckstrin-homology (PH) domain. We show here that the Lbc DH domain alone is capable of stimulating new DNA synthesis in quiescent fibroblasts and Rho-dependent actin stress fiber assembly. However, the PH domain is required for subcellular localization of Lbc along actin stress fibers and for efficient transformation of NIH3T3 cells. The results show that, in contrast to other Dbl-homology proteins, the PH domain of Lbc is dispensable for activation of Rho in vivo. The PH domain-dependent subcellular localization of Lbc may, however, be important for growth factor activation of endogenous Lbc and for oncogenic transformation.
Dbl-同源（DH）蛋白家族的成员可促进Rho GTP酶上的鸟嘌呤核苷酸交换。Lbc专门作用于Rho，而非Rac或Cdc42，它作为一种转化癌基因被分离出来，由一个DH结构域和一个普列克底物蛋白同源（PH）结构域组成。我们在此表明，单独的Lbc DH结构域能够刺激静止成纤维细胞中的新DNA合成以及Rho依赖的肌动蛋白应力纤维组装。然而，PH结构域对于Lbc沿肌动蛋白应力纤维的亚细胞定位以及NIH3T3细胞的高效转化是必需的。结果表明，与其他Dbl-同源蛋白不同，Lbc的PH结构域在体内对Rho的激活并非必需。然而，Lbc依赖PH结构域的亚细胞定位可能对内源性Lbc的生长因子激活以及致癌转化很重要。
