DISTINCT ROLES FOR DH AND PH DOMAINS IN THE LBC ONCOGENE

Members of the Dbl-homology (DH) family of proteins promote guanine nu cleotide exchange on Rho GTPases, Lbc, which specifically acts on Rho but not Rac or Cdc42, was isolated as a transforming oncogene and is c omposed of a DH and a Pleckstrin-homology (PH) domain, We show here th at the Lbc DH domain alone is capable of stimulating new DNA synthesis in quiescent fibroblasts and Rho-dependent actin stress fiber assembl y. However, the PH domain is required for subcellular localization of Lbc along actin stress fibers and for efficient transformation of NIH3 T3 cells, The results show that, in contrast to other Dbl-homology pro teins, the PH domain of Lbc is dispensable for activation of Rho in vi vo, The PH domain-dependent subcellular localization of Lbc may, howev er, be important for growth factor activation of endogenous Lbc and fo r oncogenic transformation.