Specific contributions of the small GTPases Rho, Rac, and Cdc42 to Dbl transformation.

摘要: Abstract Dbl is a representative prototype of growing family oncogene products that contain the homology/pleckstrin homology elements in their primary structures and are associated with variety neoplastic pathologies. Members have been shown to function as physiological activators (guanine nucleotide exchange factors) Rho-like small GTPases. Although expression GTPase-defective versions Rho proteins has induce transformed phenotype under different conditions, transformation capacity typically weak incomplete relative exhibited by dbl-like oncogenes. Moreover, some cases (e.g. NIH3T3 fibroblasts), Cdc42 results growth inhibition. Thus, attempting reconstitute dbl-induced fibroblasts, we generated spontaneously activated (“fast-cycling”) mutants Cdc42, Rac1, RhoA mimic functional effects activation oncoprotein. When stably expressed cells, all three caused loss serum dependence showed increased saturation density. Furthermore, stable cell lines were tumorigenic when injected into nude mice. Our data demonstrate targets need be promote full complement effects. More importantly, each these GTP-binding contributes distinct facet cellular transformation.