title: Expanding functions of GIT Arf GTPase-activating proteins, PIX Rho guanine nucleotide exchange factors and GIT-PIX complexes.
abstract: The GIT proteins, GIT1 and GIT2, are GTPase-activating proteins (inactivators) for the ADP-ribosylation factor (Arf) small GTP-binding proteins, and function to limit the activity of Arf proteins. The PIX proteins, α-PIX and β-PIX (also known as ARHGEF6 and ARHGEF7, respectively), are guanine nucleotide exchange factors (activators) for the Rho family small GTP-binding protein family members Rac1 and Cdc42. Through their multi-domain structures, GIT and PIX proteins can also function as signaling scaffolds by binding to numerous protein partners. Importantly, the constitutive association of GIT and PIX proteins into oligomeric GIT-PIX complexes allows these two proteins to function together as subunits of a larger structure that coordinates two distinct small GTP-binding protein pathways and serves as multivalent scaffold for the partners of both constituent subunits. Studies have revealed the involvement of GIT and PIX proteins, and of the GIT-PIX complex, in numerous fundamental cellular processes through a wide variety of mechanisms, pathways and signaling partners. In this Commentary, we discuss recent findings in key physiological systems that exemplify current understanding of the function of this important regulatory complex. Further, we draw attention to gaps in crucial information that remain to be filled to allow a better understanding of the many roles of the GIT-PIX complex in health and disease.
authors.affiliation: Department of Medicine, College of Medicine and Health, Lishui University, Lishui 323000, China.
authors.forename: Wu
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Computer Science and Technology, College of Engineering and Design, Lishui University, Lishui 323000, China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA richard.premont@duke.edu.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Premont
mesh_terms: D020823:ADP-Ribosylation Factor 1 / Q000235:genetics*; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D020690:GTPase-Activating Proteins / Q000235:genetics*; D006801:Humans; D046912:Multiprotein Complexes / Q000235:genetics; D011485:Protein Binding; D064067:Rho Guanine Nucleotide Exchange Factors / Q000235:genetics*; D015398:Signal Transduction; D020764:cdc42 GTP-Binding Protein / Q000235:genetics; D020830:rac1 GTP-Binding Protein / Q000235:genetics
chemical_list: C576603:ARHGEF6 protein, human; C576606:ARHGEF7 protein, human; D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C485647:GIT1 protein, human; C430213:GIT2 protein, human; D020690:GTPase-Activating Proteins; D046912:Multiprotein Complexes; D064067:Rho Guanine Nucleotide Exchange Factors; D020823:ADP-Ribosylation Factor 1; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein
keywords: ArfGAP; GIT1; GIT2; RhoGEF; α-PIX; β-PIX