Gα12/13 signaling in metabolic diseases

As the key governors of diverse physiological processes, G protein-coupled receptors (GPCRs) have drawn attention as primary targets for several diseases, including diabetes and cardiovascular disease. Heterotrimeric G proteins converge signals from ~800 members of the GPCR family. Among the members of the G protein α family, the Gα 12 family members comprising Gα 12 and Gα 13 have been referred to as gep oncogenes. Gα 12/13 levels are altered in metabolic organs, including the liver and muscles, in metabolic diseases. The roles of Gα 12/13 in metabolic diseases have been investigated. In this review, we highlight findings demonstrating Gα 12/13 amplifying or dampening regulators of phenotype changes. We discuss the molecular basis of G protein biology in the context of posttranslational modifications to heterotrimeric G proteins and the cell signaling axis. We also highlight findings providing insights into the organ-specific, metabolic and pathological roles of G proteins in changes associated with specific cells, energy homeostasis, glucose metabolism, liver fibrosis and the immune and cardiovascular systems. This review summarizes the currently available knowledge on the importance of Gα 12/13 in the physiology and pathogenesis of metabolic diseases, which is presented according to the basic understanding of their metabolic actions and underlying cellular and molecular bases. Metabolic diseases: Going after G proteins Understanding the activities of two members of a vital category of proteins called G proteins, which initiate metabolic changes when signaling molecules bind to cells, could lead to new therapies for many diseases. Researchers in South Korea and Japan, led by Sang Geon Kim at Seoul National University, review the significance of the Gα12 and Gα13 proteins in diseases characterised by significant changes in metabolism, including liver conditions and disorders of the cardiovascular and immune systems. Specific roles for the proteins have been identified by a variety of methods, including studying the effect of disabling the genes that code for them in mice. Recent insights suggest that drugs interfering with the activity of these Gα proteins might help treat many conditions in which the molecular signalling networks involving the proteins are disrupted.