Gα12- and Gα13-Subunits of Heterotrimeric G-Proteins A Novel Family of Oncogenes

Certain polypeptide growth factor receptors possess an intrinsic protein tyrosine kinase activity (1), and a large body of information implicates these receptors in normal and aberrant cell growth. As such, a number of oncogenes have been found to code for altered forms of these receptors (2–4), their ligands (5), or for molecules thought to participate in their growth-promoting pathways (6). Another family of structurally related cell-surface receptors is linked to heterotrimeric G-proteins, and this class of receptors has been traditionally linked to tissue-specific, fully differentiated cell functions, such as photoreception, chemoreception, and neurotransmission (7). However, G-protein-coupled receptors (GPCRs) are also expressed in most proliferating cells, and they have been implicated in embryogenesis and growth stimulation (8). Furthermore, the vast majority of GPCRs identified so far exhibit a common structural motif consisting of the presence of seven transmembrane-spanning domains (7), a property that was also predicted for the protein product of the mas oncogene on the basis of its nucleotide sequence (9). This finding provided the first link between cellular transformation and GPCRs.