Abstract
Heterotrimeric G-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 Gβγ-dimer in the regulation of a variety of intracellular effectors, including ion channels, adenylyl cyclase, and phospholipase Cβ. In many cases, Gβγ-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. Gβγ-dimers directly activate PI3Kγ as well as the more widely distributed PI3Kβ. The activation of PI3Kγ by Gβγ-dimers likely involves direct binding of specific Gβγ-dimers to both subunits of PI3Kγ. Thus, Gβγ-dimers transmit signals from numerous receptors to a variety of intracellular effectors in distinct cellular contexts. Five distinct Gβ-subunits and 12 distinct Gγ-subunits have been identified. New experimental approaches are needed to elucidate the specific roles of individual Gβγ-dimers in the pathways that transduce signals for proliferation and survival.
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