SIGNALING BY THE G(12) CLASS OF G-PROTEINS

The G(12) class of G proteins are defined by the a-subunits of mammali an G(12) and G(13). Biochemical and mutational characterization of G a lpha(12/13) have identified several novel signaling pathways regulated by these alpha-subunits. Studies with the constitutively activated mu tants of G alpha(12) and G alpha(13) have indicated that they stimulat e 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 modu le, Na+/H+ exchangers, focal adhesion assemblies, and transcriptional activation of specific primary response genes. The emerging view sugge sts that these signaling events represent an integrated response regul ated by G(12) and G(13). This review discusses the diverse signaling r esponses regulated by G(12) and G(13), and the interrelationship of th ese responses.