A mutant alpha subunit of G12 potentiates the eicosanoid pathway and is highly oncogenic in NIH 3T3 cells.

Abstract

The discovery of GTPase-inhibiting muta-

Cell growth control by G protein-coupled receptors: from signal transduction to signal integration

“…Activating mutations have also been identi®ed for Ga i2 , referred to as the gip2 oncogene, in a subset of ovarian sex cord stromal tumors and adrenal cortical tumors (Lyons et al, 1990). In addition, Ga 12 , referred as the gep oncogene (Xu et al, 1993(Xu et al, , 1994, was isolated as a transforming gene from a soft tissue sarcoma-derived cell (Chan et al, 1993), although its role in tumorigenesis is still unclear. No naturally occurring activated mutations in members of the Ga q family have been described to date.…”

The ras-related GTPase rac1 regulates a proliferative pathway selectively utilized by G-protein coupled receptors

“…Rac(7) and ras(7) are each dominant negative mutants which contain the mutation T17N, rendering these proteins unable to bind GTP ( see Feig and Cooper 1988) pathways (Clapham and Neer, 1993). The heterotrimeric G-proteins Gaq, Ga12 and Ga13 are each capable of transforming NIH3T3 cells (Dhanasekaran and Dermott, 1996;Voyno-Yasenetskaya et al, 1994;Chan et al, 1993;Xu et al, 1993;Jiang et al, 1993;Kalinec et al, 1992) and we have previously shown that Gaq but not Ga12 is responsible for transducing m5-induced proliferative responses in NIH3T3 cells (Burstein et al, 1995b;. It has been recently shown that GTPase de®cient mutants of Gaq, Ga12 and Ga13 activate the JNK pathway (VoynoYasenetskaya et al, 1996;Vara Prasad et al, 1995) and we have found that Gaq, Ga12 and Ga13 can each induce proliferative responses in R-SAT TM (Figure 1 and see Burstein et al, 1997).…”

The Src family tyrosine kinase is involved in Rho-dependent activation of c-Jun N-terminal kinase by Gα12

“…Overexpression of wild-type Ga 12 transforms NIH3T3 cells (Chan et al, 1993), and expression of Ga 12 Q229L or Ga 13 Q226L induces neoplastic transformation in NIH3T3 cells (Xu et al, 1993(Xu et al, , 1994Jiang et al, 1993;Vara Prasad et al, 1994) and Rat-1 cells . In 1321N1 astrocytoma cells, Ga 12 is required for thrombin-induced mitogenesis (Aragay et al, 1995).…”