ACTIVATED MUTANT OF G-ALPHA(13) INDUCES EGR-1, C-FOS, AND TRANSFORMATION IN NIH 3T3 CELLS

Expression of the constitutively activated mutant alpha-subunit of the heterotrimeric G protein G alpha(13) (alpha(13)Q226L) leads to the tr ansformation of NIH-3T3 cells. An analysis of the mitogenic pathway me diated by alpha(13)Q226L indicated that the expression of the primary response genes, early growth response gene-1 (Egr-1, a nuclear transcr iption factor with zinc-finger moth) and c-fos (a leucine zipper trans cription factor as well as a protooncogene) are constitutively activat ed in alpha(13)Q226L-transformants. While ras-transformed cells did no t express Egr-1, cells transformed by the GTPase deficient mutant a-su bunit of G alpha(12) (alpha(12)Q229L) exhibited a ''weak'' expression, suggesting that the induction of Egr-1 and c-fos is intrinsic to G al pha(13) signaling pathway and not a consequence of the transformed phe notype. Taken together, these results provide the first evidence that the G alpha(13) signaling pathway involves the activation of specific transcription factors and defines the expression of these nuclear tran scription factors as a possible molecular mechanism in alpha(13)Q226L- mediated cell proliferation and transformation.