Signaling by the G(12) class of G proteins

The G(12) class of G proteins are defined by the a-subunits of mammalian G(12) and G(13). Biochemical and mutational characterization of G alpha(12/13) have identified several novel signaling pathways regulated by these alpha-subunits. Studies with the constitutively activated mutants of G alpha(12) and G alpha(13) have indicated that they stimulate mitogenic signaling pathways leading to the oncogenic transformation of fibroblast cell lines. Recent analyses have indicated that G alpha(12) and G alpha(13) regulate cytoplasmic as well as nuclear signaling events such as activation of the Jun N-terminal kinase signaling module, Na+/H+ exchangers, focal adhesion assemblies, and transcriptional activation of specific primary response genes. The emerging view suggests that these signaling events represent an integrated response regulated by G(12) and G(13). This review discusses the diverse signaling responses regulated by G(12) and G(13), and the interrelationship of these responses.