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 (α, β, γ) and are subdivided into four families, Gαi, Gα12/13, Gαq, and Gαs. These proteins cycle between an inactive Gα-GDP state and active Gα-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 Gαi family. This family has the largest number of individual members, including Gαi1, Gαi2, Gαi3, Gαo, Gαt, Gαg, and Gαz, and constitutes the majority of G proteins α subunits expressed in a tissue or cell. Gαi 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 Gαi 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.