Activation of Rac1, RhoA, and Mitogen-Activated Protein Kinases Is Required for Ras Transformation

• DOI: 10.1128/mcb.15.11.6443
• Publication Date: 2015-10-09T00:18:10Z
• Authors: Roya Khosravi-Far; Patricia A. Solski; Geoffrey J. Clark; Michael S. Kinch; Channing J. Der
• Keywords: Small GTPase

Although substantial evidence supports a critical role for the activation of Raf-1 and mitogen-activated protein kinases (MAPKs) in oncogenic Ras-mediated transformation, recent suggests that Ras may activate second signaling pathway which involves Ras-related proteins Rac1 RhoA. Consequently, we used three complementary approaches to determine contribution RhoA function transformation. First, whereas constitutively activated mutants showed very weak transforming activity when transfected alone, their coexpression with weakly mutant caused greater than 35-fold enhancement activity. Second, observed dominant negative reduced Third, further enhanced Ras-triggered morphologic as well growth soft agar cell motility. Finally, also kinase-deficient MAPKs inhibited Taken together, these data support possibility RhoA, coupled Raf/MAPK pathway, is required trigger full morphogenic mitogenic consequences