Physiological functions and structural features of Gα12/13 proteins

Abstract

Heterotrimeric G proteins are pivotal signal transduction molecules that propagate extracellular signals through G protein-coupled receptors (GPCRs) in the cell. Receptor activation initiates diverse signaling cascades depending on the associated G protein, particularly its Gα subunit, which determines assignment to either the Gαs/olf, Gαi/o, Gαq/11, or Gα12/13 family. The downstream signaling pathways of the families Gαs/olf, Gαi/o, and Gαq/11 have been explored to a greater extent than Gα12/13. The Gα12/13 family interacts with Rho GTPases and thereby regulates physiological functions such as cell migration, cell adhesion, cytoskeletal changes, cell proliferation, transformation, angiogenesis, and embryonic development. Dysregulation and overexpression of this Gα protein family has been implicated in the pathogenesis of disorders such as asthma, cardiovascular diseases, and cancer. In view of the crucial functions, in-depth insights into the signaling pathways and structural properties of the Gα12/13 family are essential for their full characterization and for elucidating their role as potential targets for drug research. This review summarizes the key findings reported so far and emphasizes the importance of a thorough investigation of the Gα12/13 family drawing attention to the lacunae regarding their signaling and structural attributes.