Regulation and physiological functions of G12/13-mediated signaling pathways.
Accumulating data indicate that G12 subfamily (Galpha12/13)-mediated signaling pathways play pivotal roles in a variety of physiological processes, while aberrant regulation of this pathway has been identified in various human diseases. It has been demonstrated that Galpha12/13-mediated signals form networks with other signaling proteins at various levels, from cell surface receptors to transcription factors, to regulate cellular responses. Galpha12/13 have slow rates of nucleotide exchange and GTP hydrolysis, and specifically target RhoGEFs containing an amino-terminal RGS homology domain (RH-RhoGEFs), which uniquely function both as a GAP and an effector for Galpha12/13. In this review, we will focus on the mechanisms regulating the Galpha12/13 signaling system, particularly the Galpha12/13-RH-RhoGEF-Rho pathway, which can regulate a wide variety of cellular functions from migration to transformation.
Suzuki
Nobuchika
N
Laboratory of Systems Biology and Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan. suzuki-n@lsbm.org
Hajicek
Nicole
N
Kozasa
Tohru
T
D000818:Animals; D002318:Cardiovascular Diseases / Q000378:metabolism; D020555:GTP-Binding Protein Regulators / Q000378:metabolism; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006801:Humans; D007107:Immune System / Q000502:physiology; D009369:Neoplasms / Q000378:metabolism; D015398:Signal Transduction; D018411:Spodoptera; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D020555:GTP-Binding Protein Regulators; D020662:Guanine Nucleotide Exchange Factors; D044365:GTP-Binding Protein alpha Subunits, G12-G13; D020741:rho GTP-Binding Proteins