|
|
|
|
|
||
|
|||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | |||||
First published online April 5, 2006
doi: 10.1242/10.1242/jcs.02925
Commentary |
Cardiovascular Research Institute and Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA
* Author for correspondence (e-mail: bradford_berk{at}urmc.rochester.edu)
Accepted 6 February 2006
The G-protein-coupled receptor (GPCR)-kinase-interacting proteins 1 and 2 (GIT1 and GIT2) are ubiquitous multidomain proteins involved in diverse cellular processes. They traffic between three distinct cellular compartments (cytoplasmic complexes, focal adhesions and the cell periphery) through interactions with proteins including ARF, Rac1 and Cdc42 GTPases, p21-activated kinase (PAK), PAK-interacting exchange factor (PIX), the kinase MEK1, phospholipase C
(PLC) and paxillin. GITs and PIX cooperate to form large oligomeric complexes to which other proteins are transiently recruited. Activation of Rac1 and Cdc42 drives association of PAK with these oligomers, which unmasks the paxillin-binding site in GITs that recruits them to focal complexes. There, they regulate cytoskeletal dynamics by feedback inhibition of Rac1. GITs also participate in receptor internalization by regulating membrane trafficking between the plasma membrane and endosomes, targeting ARF GTPases through their ARF GTPase-activating protein (ARF-GAP) activity. Furthermore, GITs act as scaffolds to control spatial activation of several signaling molecules. Finally, recent results suggest pathogenic roles for GIT proteins in Huntington's disease and HIV infection.
Key words: GIT1, G-protein-coupled receptor, Endosomes, Phospholipase C
This article has been cited by other articles:
|
|
 |
|
  S. Nola, M. Sebbagh, S. Marchetto, N. Osmani, C. Nourry, S. Audebert, C. Navarro, R. Rachel, M. Montcouquiol, N. Sans, et al. Scrib regulates PAK activity during the cell migration process Hum. Mol. Genet., November 15, 2008; 17(22): 3552 - 3565. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. J. Baugher and A. Richmond The Carboxyl-terminal PDZ Ligand Motif of Chemokine Receptor CXCR2 Modulates Post-endocytic Sorting and Cellular Chemotaxis J. Biol. Chem., November 7, 2008; 283(45): 30868 - 30878. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Kahn, E. Bruford, H. Inoue, J. M. Logsdon Jr., Z. Nie, R. T. Premont, P. A. Randazzo, M. Satake, A. B. Theibert, M. L. Zapp, et al. Consensus nomenclature for the human ArfGAP domain-containing proteins J. Cell Biol., September 22, 2008; 182(6): 1039 - 1044. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. M. Zhang, J. A. Simmerman, C. D. Guibao, and J. J. Zheng GIT1 Paxillin-binding Domain Is a Four-helix Bundle, and It Binds to Both Paxillin LD2 and LD4 Motifs J. Biol. Chem., July 4, 2008; 283(27): 18685 - 18693. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Missy, B. Hu, K. Schilling, A. Harenberg, V. Sakk, K. Kuchenbecker, K. Kutsche, and K.-D. Fischer {alpha}PIX Rho GTPase Guanine Nucleotide Exchange Factor Regulates Lymphocyte Functions and Antigen Receptor Signaling Mol. Cell. Biol., June 1, 2008; 28(11): 3776 - 3789. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Pang, C. Yan, K. Natarajan, M. E. Cavet, M. P. Massett, G. Yin, and B. C. Berk GIT1 Mediates HDAC5 Activation by Angiotensin II in Vascular Smooth Muscle Cells Arterioscler. Thromb. Vasc. Biol., May 1, 2008; 28(5): 892 - 898. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kruger, I. Kratchmarova, B. Blagoev, Y.-H. Tseng, C. R. Kahn, and M. Mann Dissection of the insulin signaling pathway via quantitative phosphoproteomics PNAS, February 19, 2008; 105(7): 2451 - 2456. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. J. Cuthbert, K. K. Davis, and J. E. Casanova Substrate specificities and activities of AZAP family Arf GAPs in vivo Am J Physiol Cell Physiol, January 1, 2008; 294(1): C263 - C270. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Totaro, S. Paris, C. Asperti, and I. de Curtis Identification of an Intramolecular Interaction Important for the Regulation of GIT1 Functions Mol. Biol. Cell, December 1, 2007; 18(12): 5124 - 5138. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Janz, T. P. Sakmar, and K. C. Min A Novel Interaction between Atrophin-interacting Protein 4 and beta-p21-activated Kinase-interactive Exchange Factor Is Mediated by an SH3 Domain J. Biol. Chem., September 28, 2007; 282(39): 28893 - 28903. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. P. Jones and M. Katan Role of Phospholipase C{gamma}1 in Cell Spreading Requires Association with a {beta}-Pix/GIT1-Containing Complex, Leading to Activation of Cdc42 and Rac1 Mol. Cell. Biol., August 15, 2007; 27(16): 5790 - 5805. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Virag and S. D. Harris Functional Characterization of Aspergillus nidulans Homologues of Saccharomyces cerevisiae Spa2 and Bud6 Eukaryot. Cell, June 1, 2006; 5(6): 881 - 895. [Abstract] [Full Text] [PDF]
|
|
