Mutated alpha subunit of the Gq protein induces malignant transformation in NIH 3T3 cells.
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.
Kalinec
G
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Laboratory of Cellular Development and Oncology, National Institute of Dental Research, Bethesda, Maryland 20892.
Nazarali
A J
AJ
Hermouet
S
S
Xu
N
N
Gutkind
J S
JS
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004247:DNA; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000235:genetics* / Q000502:physiology; D007295:Inositol Phosphates / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009368:Neoplasm Transplantation; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D054801:Phosphoinositide Phospholipase C; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D014162:Transfection
D007295:Inositol Phosphates; D004247:DNA; D010727:Phosphoric Diester Hydrolases; D054801:Phosphoinositide Phospholipase C; D019204:GTP-Binding Proteins; D043265:Phosphatidylinositol Diacylglycerol-Lyase