Heterotrimeric G-protein βγ-dimers in growth and differentiation

Heterotrimeric C-proteins are components of the signal transduction pathways for the soluble and cell-contact signals that regulate normal growth and differentiation. There is now a greater appreciation of the role of the G beta gamma -dimer in the regulation of a variety of intracellular effecters, including ion channels, adenylyl cyclase, and phospholipase C beta, In many cases, G beta gamma -dimers are required for the activation of mitogen activated protein kinase (MAPK) pathways that promote cellular proliferation, although the underlying mechanisms have yet to be fully elucidated, Activation of phosphotidylinositol-3-kinase (PI3K) is a critical step in the intracellular transduction of survival signals. G beta gamma -dimers directly activate PI3K gamma as well as the more widely distributed PI3K beta. The activation of PI3K gamma by G beta gamma -dimers likely involves direct binding of specific G beta gamma -dimers to both subunits of PI3K gamma. Thus, G beta gamma -dimers transmit signals from numerous receptors to a variety of intracellular effecters in distinct cellular contexts. Five distinct G beta -subunits and 12 distinct G gamma -subunits have been identified. New experimental approaches are needed to elucidate the specific roles of individual G beta gamma -dimers in the pathways that transduce signals for proliferation and survival.