Gαi protein subunit: A step toward understanding its non-canonical mechanisms

The heterotrimeric G protein family plays essential roles during a varied array of cellular events; thus, its deregulation can seriously alter signaling events and the overall state of the cell. Heterotrimeric G-proteins have three subunits (alpha, beta, gamma) and are subdivided into four families, G alpha i, G alpha 12/13, G alpha q, and G alpha s. These proteins cycle between an inactive G alpha-GDP state and active G alpha-GTP state, triggered canonically by the G-protein coupled receptor (GPCR) and by other accessory proteins receptors independent also known as AGS (Activators of G-protein Signaling). In this review, we summarize research data specific for the G alpha i family. This family has the largest number of individual members, including G alpha i1, G alpha i2, G alpha i3, G alpha o, G alpha t, G alpha g, and G alpha z, and constitutes the majority of G proteins alpha subunits expressed in a tissue or cell. G alpha i was initially described by its inhibitory function on adenylyl cyclase activity, decreasing cAMP levels. Interestingly, today Gi family G-protein have been reported to be importantly involved in the immune system function. Here, we discuss the impact of G alpha i on non-canonical effector proteins, such as c-Src, ERK1/2, phospholipase-C (PLC), and proteins from the Rho GTPase family members, all of them essential signaling pathways regulating a wide range of physiological processes.