Türk Biyokimya Dergisi (May 2007)
Heterotrimeric G Proteins
Abstract
Heterotrimeric G proteins, commonly known as G proteins are members of thelarge GTPase superfamily that are conserved from bacteria to mammals. G proteinsplay an essential role in cellular signaling by coupling many cell surface receptorsto effectors on the plasma membrane. G proteins are composed of an α-subunit thatbinds and hydrolyzes GTP and a βγ-subunit complex. To date over 20 different αsubunits, 5 β subunits and 14 γ subtypes have been defined. Classification of Gprotein heterotrimers are based on the primary sequences of their α-subunits, resultingin four main families. In its inactive state, each G protein is a heterotimer inwhich the GDP bound α chain is tightly associated with the βγ subunits. Receptoractivation promotes the replacement of GDP by GTP and the consequent dissociationof α from βγ. Both αGTP and the βγ complex interact with and regulate specificeffectors. Activation is then terminated by the intrinsic GTPase activity of the αchain, which returns the protein to its inactive state. G proteins are regulated byposttranslational modifications including phosphorylation, myristoylation, palmitoylation,and prenylation of Gα- and Gβγ- subunits. G protein α- and βγ- subunitsregulate the activities of diverse effectors. G proteins mediate a wide variety ofcellular responses, including sensory perception, neuronal activity and hormonalregulation. Recent reports indicate that GPCRs and G proteins are also involved inthe regulation of cell growth, differentiation and cellular transformation
