Open AccessMutated alpha subunit of the Gq protein induces malignant transformation in NIH 3T3 cells.
Author(s) -
Gilda M. Kalinec,
Adil J. Nazarali,
Sylvie Hermouet,
Ningzhi Xu,
J. Silvio Gutkind
Publication year - 1992
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.12.10.4687
Subject(s) - heterotrimeric g protein , biology , adenylyl cyclase , g alpha subunit , gs alpha subunit , g protein , gtp binding protein regulators , gtpase activating protein , microbiology and biotechnology , protein subunit , gq alpha subunit , gi alpha subunit , gtpase , phospholipase c , signal transduction , biochemistry , gene
The discovery of mutated, GTPase-deficient alpha subunits of Gs or Gi2 in certain human endocrine tumors has suggested that heterotrimeric G proteins play a role in the oncogenic process. Expression of these altered forms of G alpha s or G alpha i2 proteins in rodent fibroblasts activates or inhibits endogenous adenylyl cyclase, respectively, and causes certain alterations in cell growth. However, it is not clear whether growth abnormalities result from altered cyclic AMP synthesis. In the present study, we asked whether a recently discovered family of G proteins, Gq, which does not affect adenylyl cyclase activity, but instead mediates the activation of phosphatidylinositol-specific phospholipase C harbors transforming potential. We mutated the cDNA for the alpha subunit of murine Gq in codons corresponding to a region involved in binding and hydrolysis of GTP. Similar mutations unmask the transforming potential of p21ras or activate the alpha subunits of Gs or Gi2. Our results show that when expressed in NIH 3T3 cells, activating mutations convert G alpha q into a dominant acting oncogene.