The Roles of Guanine Nucleotide Binding Proteins in Health and Disease

Abstract

G-proteins are important mediators of cellular and tissue functions and are characterised by a recognition site for Guanine Triphosphate (GTP), Guanine Diphosphate (GDP) and possess intrinsic GTPase activity. They play important roles in signal transduction responsible for cytoskeletal remodelling, cellular differentiation and vesicular transport. They are made up of three types namely, the small G-proteins, the sensors and the heterotrimeric G-proteins. The G-protein heterotrimers consist of G-alpha (G), G-beta (G$) and G-gamma (G() subunits. Each heterotrimeric G-protein have different subunits and the combination of these subunits define the specific role of each G-protein. The activation of G subunits regulates the activity of effector enzymes and ion channels while G$( subunits function in the regulation of mitogen-activated protein kinase (MAP-kinase) pathway. The G-protein-mediated signal transduction is important in the regulation of a cells morphological and physiological response to external stimuli. MAPKs are involved in the phosphorylation of transcription factors that stimulate gene transcription. Gs stimulates adenylate cyclase, thereby increasing cyclic adenosine monophosphate (cAMP) leading to the phosphorylation and subsequent activation of Ca_+ channels. G proteins are involved in disease pathology through several mechanisms which interfere with the G protein activity. Other disease pathologies associated with abnormal mutations in G proteins can interfere with signal transduction pathways which may involve signal transmission that is either excessive, by augmentation of G protein function, or insufficient, via inactivation of G proteins.