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 13Q226L) leads to the transformation of NIH-3T3 cells. An analysis of the mitogenic pathway mediated by alpha 13Q226L indicated that the expression of the primary response genes, early growth response gene-1 (Egr-1, a nuclear transcription factor with zinc-finger motif) and c-fos (a leucine zipper transcription factor as well as a protooncogene) are constitutively activated in alpha 13Q226L-transformants. While ras-transformed cells did not express Egr-1, cells transformed by the GTPase deficient mutant alpha-subunit of G alpha 12 (alpha 12Q229L) exhibited a "weak" expression, suggesting that the induction of Egr-1 and c-fos is intrinsic to G alpha 13 signaling pathway and not a consequence of the transformed phenotype. 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 transcription factors as a possible molecular mechanism in alpha 13Q226L-mediated cell proliferation and transformation.
Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA 19140.
M V
MV
Vara Prasad
S K
SK
Shore
N
N
Dhanasekaran
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic; D004268:DNA-Binding Proteins / Q000235:genetics*; D051766:Early Growth Response Protein 1; D019204:GTP-Binding Proteins / Q000502:physiology*; D005786:Gene Expression Regulation; D016762:Genes, fos; D017874:Immediate-Early Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D011493:Protein Kinase C / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D017874:Immediate-Early Proteins; D014157:Transcription Factors; D011493:Protein Kinase C; D019204:GTP-Binding Proteins