A mutant alpha subunit of Gi2 induces neoplastic transformation of Rat-1 cells.
AUTOR(ES)
Pace, A M
RESUMO
In a recently discovered class of oncogenes, GTPase-inhibiting mutations constitutively activate alpha subunits of signal-transducing guanine nucleotide-binding proteins (G proteins). Somatic mutations in a subclass of endocrine tumors are found in the arginine-179 codon of the alpha subunit of Gi2 (alpha i2), creating the putative gip2 oncogene. We have tested the ability of gip2 to mediate neoplastic transformation of Rat-1 and NIH 3T3 fibroblasts in tissue culture. Expression of a mutant alpha i2 cDNA encoding cysteine in place of arginine-179 (alpha i2-R179C) caused Rat-1 cells to grow to a higher density in monolayer culture, to lose anchorage dependence, and to form tumors when injected subcutaneously into nude mice. In contrast, expression of alpha i2-R179C failed to alter growth or tumorigenicity of NIH 3T3 cells. We conclude that gip2 is an oncogene, by the criterion that it induces neoplastic transformation of Rat-1 cells. Failure of gip2 to transform NIH 3T3 cells is in keeping with clinical indications that gip2 is a tissue-selective oncogene.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=52227Documentos Relacionados
- Activating and inactivating mutations of the alpha subunit of Gi2 protein have opposite effects on proliferation of NIH 3T3 cells.
- Adenylyl cyclase inhibition and altered G protein subunit expression and ADP-ribosylation patterns in tissues and cells from Gi2 alpha-/-mice.
- Mutated alpha subunit of the Gq protein induces malignant transformation in NIH 3T3 cells.
- Gi2 and protein kinase C are required for thyrotropin-releasing hormone-induced stimulation of voltage-dependent Ca2+ channels in rat pituitary GH3 cells.
- Transformation of Rat-1 fibroblasts with the v-src oncogene increases the tyrosine phosphorylation state and activity of the alpha subunit of Gq/G11.
