Gα(12) and Gα(13): Versatility in Physiology and Pathology

G protein-coupled receptors (GPCRs), as the largest family of receptors in the human body, are involved in the pathological mechanisms of many diseases. Heterotrimeric G proteins represent the main molecular switch and receive cell surface signals from activated GPCRs. Growing evidence suggests that Gα(12) subfamily (Gα(12/13))-mediated signaling plays a crucial role in cellular function and various pathological processes. The current research on the physiological and pathological function of Gα(12/13) is constantly expanding, Changes in the expression levels of Gα(12/13) have been found in a wide range of human diseases. However, the mechanistic research on Gα(12/13) is scattered. This review briefly describes the structural sequences of the Gα(12/13) isoforms and introduces the coupling of GPCRs and non-GPCRs to Gα(12/13). The effects of Gα(12/13) on RhoA and other signaling pathways and their roles in cell proliferation, migration, and immune cell function, are discussed. Finally, we focus on the pathological impacts of Gα(12/13) in cancer, inflammation, metabolic diseases, fibrotic diseases, and circulatory disorders are brought to focus.