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GIT Proteins: Arf Gaps and Signaling Scaffolds

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ARF Family GTPases

Part of the book series: Proteins and Cell Regulation ((PROR,volume 1))

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Abstract

GIT proteins are GTPase-activating proteins (GAPs) for the ADP-ribosylation factor (Arf) family of GTPases. The two GIT family members, GIT1 and GIT2, stimulate GTP hydrolysis on all the known Arf subtypes about equally well, and this activity is stimulated by PI(3,4,5)P3. As such, GITs are negative regulators of the cellular functions of Arfs, such as intracellular vesicle traffic and cytoskeletal rearrangement. In addition, GITs form the core of a large protein complex involved in integrating signals through multiple pathways, involving G protein-coupled receptors, receptor tyrosine kinases, integrins, and at least two classes of small GTP-binding proteins, the Arfs and Rac/Cdc42, Rho families.

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References

  • Antonny, B., Huber, I., Paris, S., Chabre, M., and Cassel, D. (1997). Activation of ADP-ribosylation factor 1 GTPase-activating protein by phosphatidylcholine-derived diacylglycerols. J. Biol. Chem., 272, 30848–30851.

    Article  CAS  PubMed  Google Scholar 

  • Bagrodia, S., Bailey, D., Lenard, Z., Hart, M., Guan, J. L., Premont, R. T., Taylor, S. J., and Cerione, R. A. (1999). A tyrosine-phosphorylated protein that binds to an important regulatory region on the Cool family of p21-activated kinase-binding proteins. J. Biol. Chem., 274, 22393–22400.

    Article  CAS  PubMed  Google Scholar 

  • Brown, M. C., West, K. A., and Turner, C. E. (2002). Paxillin-dependent paxillin kinase linker and p21-activated kinase localization to focal adhesions involves a multi-step activation pathway. Mol. Biol. Cell, 13, 1550–65.

    Article  CAS  PubMed  Google Scholar 

  • Claing, A., Perry, S. J., Archilio, M., Walker, J. K. L., Albanesi, J. P., Lefkowitz, R. J., and Premont, R. T. (2000). Multiple endocytic pathways of G protein-coupled receptors delineated by GIT1 sensitivity. Proc. Natl. Acad. Sci., USA, 97, 1119–24.

    Article  CAS  PubMed  Google Scholar 

  • Claing, A., Chen, W., Miller, W. E., Vitale, N., Moss, J., Premont, R. T., and Lefkowitz, R. J. (2001). β-Arrestin-mediated ADP-ribosylation factor 6 activation and β2-adrenergic receptor endocytosis. J. Biol. Chem., 276, 42509–13.

    Article  CAS  PubMed  Google Scholar 

  • Cukierman, E., Huber, I., Rotman, M., and Cassel, D. (1995). The ARF1 GTPase-activating protein: zinc finger motif and Golgi complex localization. Science, 270, 1999–2002.

    CAS  PubMed  Google Scholar 

  • de Curtis, I. (2001). Cell migration: GAPs between membrane traffic and the cytoskeleton. EMBO Reports, 2, 277–281

    PubMed  Google Scholar 

  • Di Cesare, A., Paris, S., Albertinazzi, C., Dariozzi, S., Andersen, J., Mann, M., Longhi, R., and de Curtis, I. (2000). p95-APP1 links membrane transport to Rac-mediated reorganization of actin. Nature Cell Biol., 2, 521–530.

    PubMed  Google Scholar 

  • D’Souza-Schorey, C., Li, G., Colombo, M. I., and Stahl, P. D. (1995). A regulatory role for ARF6 in receptor-mediated endocytosis. Science, 267, 1175–1178.

    Google Scholar 

  • Feng, Q., Albeck, J. G., Cerione, R. A., and Yang, W. (2002). Regulation of the Cool/Pix proteins. J. Biol. Chem., 277, 5644–5650.

    CAS  PubMed  Google Scholar 

  • Goldberg, J. (1999). Structural and functional analysis of the ARF1-ARFGAP complex reveals a role for coatomer in GTP hydrolysis. Cell, 96, 893–902.

    Article  CAS  PubMed  Google Scholar 

  • Hashimoto, S., Tsubouchi, A., Mazaki, Y., and Sabe, H. (2001). Interaction of paxillin with p21-activated kinase (PAK). J. Biol. Chem., 276, 6037–6045.

    CAS  PubMed  Google Scholar 

  • Jackson, T. R., Brown, F. D., Nie, Z., Miura, K., Foroni, L., Sun, J., Hsu, V. W., Donaldson, J. G., and Randazzo, P. A. (2000a). ACAPs are Arf6 GTPase-activating proteins that function in the cell periphery. J. Cell. Biol., 151, 627–638.

    Article  CAS  PubMed  Google Scholar 

  • Jackson, T. R., Kearns, B. G., and Theibert, A. B. (2000b). Cytohesins and centaurins: mediators of PI 3-kinase-regulated Arf signaling. Trends Biochem. Sci., 25, 489–495.

    Article  CAS  PubMed  Google Scholar 

  • Kawachi, H., Fujikawa, A., Maeda, N., and Noda, M. (2001). Identification of GIT1/Cat-1 as a substrate molecule of protein tyrosine phosphatase ζ/β by the yeast substrate-trapping system. Proc. Natl. Acad. Sci., USA, 98, 6593–6598.

    Article  CAS  PubMed  Google Scholar 

  • Kim, S., Lee, S.-H., and Park, D. (2001). Leucine zipper-mediated homodimerization of the p21-activated kinase-interacting factor, βPIX. J. Biol. Chem., 276, 10581–10584.

    CAS  PubMed  Google Scholar 

  • Koh, C.-G., Tan, E.-J., Manser, E., and Lim, L. (2002). The p21-activated kinase PAK is negatively regulated by POPX1 and POPX2, a pair of serine/threonine phosphatases of the PP2C family. Current Biol., 12, 317–321.

    CAS  Google Scholar 

  • Krugmann, S., Anderson, K. E., Ridley, S. H., Risso, N., McGregor, A., Coadwell, J., Davidson, K., Eguinoa, A., Ellson, C. D., Lipp, P., Manifava, M., Ktistakis, N., Painter, G., Thuring, J. W., Cooper, M. A., Lim, Z.-Y., Holmes, A. B., Dove, S. K., Michell, R. H., Grewal, A., Nazarian, A., Erdjument-Bromage, H., Tempst, P., Stephens, L. R., and Hawkins, P. T. (2002). Identification of ARAP3, a novel PI3K effector regulating both Arf and Rho GTPases, by selective capture on phosphoinositide affinity matrices. Mol. Cell, 9, 95–108.

    Article  CAS  PubMed  Google Scholar 

  • Ku, G. M., Yablonski, D., Manser, E., Lim, L., and Weiss, A. (2001). A PAK1-PIX-PKL complex is activated by the T-cell receptor independent of Nck, Slp-76 and LAT. EMBO J., 20, 457–465.

    Article  CAS  PubMed  Google Scholar 

  • Lefkowitz, R.J. (1998). G protein-coupled receptors. J. Biol. Chem., 273, 18677–18680.

    Article  CAS  PubMed  Google Scholar 

  • Lefkowitz, R. J. (2000). The superfamily of heptahelical receptors. Nature Cell Biol., 2, E133–E136.

    Article  CAS  PubMed  Google Scholar 

  • Lu, P.J., and Chen, C.S. (1997). Selective recognition of phosphatidylinositol 3,44,5-trisphosphate by a synthetic peptide. J. Biol. Chem., 272, 466–472.

    CAS  PubMed  Google Scholar 

  • Manabe, R., Kovalenko, M., Webb, D., and Horwitz, A. R. (2002). GIT1 functions in a motile, multi-molecular signaling complex that regulates protrusive activity and cell migration. J. Cell Sci., 115, 1497–1510.

    CAS  PubMed  Google Scholar 

  • Mandiyan, V., Andreev, J., Schlessinger, J., and Hubbard, S. R. (1999). Crystal structure of the ARF-GAP domain and ankyrin repeats of PYK2-associated protein beta. EMBO J., 18, 6890–6898.

    Article  CAS  PubMed  Google Scholar 

  • Manser, E., Loo, T.-H., Koh, C.-G., Zhao, Z.-S., Chen, X.-Q., Tan, L., Tan, I., Leung, T., and Lim, L. (1998). PAK kinases are directly coupled to the PIX family of nucleotide exchange factors. Mol. Cell, 1, 183–192.

    Article  CAS  PubMed  Google Scholar 

  • Matafora, V., Paris, S., Dariozzi, S., and de Curtis, I. (2001). Molecular mechanisms regulating the subcellular localization of p95-APP1 between the endosomal recycling compartment and sites of actin organization at the cell surface. J. Cell Sci., 114, 4509–4520.

    CAS  PubMed  Google Scholar 

  • Mazaki, Y., Hashimoto, S., Okawa, K., Tsubouchi, A., Nakamura, K., Yagi, R., Yano, H., Kondo, A., Iwamatsu, A., Mizoguchi, A., and Sabe, H. (2001). An ADP-ribosylation factor GTPase-activating protein GIT2-short/KIAA0148 is involved in subcellular localization of paxillin and actin cytoskeletal organization. Mol. Biol. Cell, 12, 645–662.

    CAS  PubMed  Google Scholar 

  • McCarty, J. H. (1998). The Nck SH2/SH3 adaptor protein: a regulator of multiple intracellular signal transduction events. BioEssays, 20, 913–921.

    Article  CAS  PubMed  Google Scholar 

  • Meng, K., Rodriguez-Pena, A., Dimitrov, T., Chen, W., Yamin, M., Noda, M., and Deuel, T.F. (2000). Pleiotrophin signals increased tyrosine phosphorylation of β-catenin through inactivation of the intrinsic catalytic activity of the receptor-type protein phosphatase β/ζ. Proc. Natl. Acad. Sci., USA, 97, 2603–2608.

    CAS  PubMed  Google Scholar 

  • Miura, K., Jacques, K. M., Stauffer, S., Kubosaki, A., Zhu, K., Hirsch, D. S., Resau, J., Zheng, Y., and Randazzo, P. A. (2002). ARAP1: a point of convergence for Arf and Rho signaling. Mol. Cell, 9, 109–119.

    Article  CAS  PubMed  Google Scholar 

  • Nagase, T., Seki, N., Tanaka, A., Ishikawa, K., and Nomura, N. (1995). Prediction of the coding sequences of unidentified human genes. DNA Res., 2, 167–174.

    CAS  PubMed  Google Scholar 

  • Nishiya, N., Shirai, T., Suzuki, W. and Nose, K. (2002). Hic-5 interacts with GIT1 with a different binding mode from paxillin. J. BioChem., 132, 279–289.

    CAS  PubMed  Google Scholar 

  • Norman, J. C., Jones, D., Barry, S. T., Holt, M. R., Cockcroft, S., and Critchley, D. R. (1998). ARF1 mediates paxillin recruitment to focal adhesions and potentiates Rho-stimulated stress fiber formation in intact and permeabilized Swiss 3T3 fibroblasts. J. Cell Biol., 143, 1981–1995.

    Article  CAS  PubMed  Google Scholar 

  • Paris, S., Za, L., Sporchia, B., and de Curtis, I. (2002). Analysis of the subcellular distribution of avian p95-APP2, an ARF-GAP orthologous to mammalian paxillin kinase linker. Int. J. Biochem. Cell Biol., 34, 826–837.

    Article  CAS  PubMed  Google Scholar 

  • Pierce, K. L., Premont, R. T., and Lefkowitz, R. J. (2002). Seven-transmembrane receptors. Nature Rev. Mol. Cell Biol., 3, 639–650.

    Article  CAS  Google Scholar 

  • Pitcher, J. A., Friedman, N. J. and Lefkowitz, R. J. (1998). G protein-coupled receptor kinases. Ann. Rev. BioChem., 67, 653–692.

    CAS  PubMed  Google Scholar 

  • Premont, R. T., Claing, A., Vitale, N., Freeman, J. L. R., Pitcher, J. A., Patton, W. A., Moss, J., Vaughan, M., and Lefkowitz, R. J. (1998). β2-Adrenergic receptor regulation by GIT1, a G protein-coupled receptor kinase-associated ADP-ribosylation factor GTPase-activating protein. Proc. Natl. Acad. Sci., USA, 95, 14082–14087.

    Article  CAS  PubMed  Google Scholar 

  • Premont, R. T., Claing, A., Vitale, N., Perry, S. J., and Lefkowitz, R. J. (2000). The GIT family of ADP-ribosylation factor GTPase-activating proteins. J. Biol. Chem., 275, 22373–22380.

    Article  CAS  PubMed  Google Scholar 

  • Randazzo, P. A. (1997). Resolution of two ADP-ribosylation factor 1 GTPase-activating proteins from rat liver. Biochem. J., 324, 413–419.

    CAS  PubMed  Google Scholar 

  • Randazzo, P. A., Andrade, J., Miura, K., Brown, M. T., Long, Y.-Q., Stauffer, S., Roller, P., and Cooper, J. A. (2000). The Arf GTPase-activating protein ASAP1 regulates the actin cytoskeleton. Proc. Natl. Acad. Sci., USA, 97, 4011–4016.

    Article  CAS  PubMed  Google Scholar 

  • Roemer, T., Vallier, L., Sheu Y.J., and Snyder, M. (1998). The Spa2-related protein, Sph1p, is important for polarized growth in yeast. J. Cell. Sci., 111, 479–494.

    CAS  PubMed  Google Scholar 

  • Scheffzek, K., Ahmadian, M. R., and Wittinghofer, A. (1998). GTPase-activating proteins: helping hands to complement an active site. Trends Biochem. Sci., 23, 257–262.

    Article  CAS  PubMed  Google Scholar 

  • Sheu, Y. J., Santos, B., Fortin, N., Costigan, C., and Snyder, M. (1998). Spa2p interacts with cell polarity proteins and signaling components involved in yeast morphogenesis. Mol. Cell Biol., 18, 4053–4069.

    CAS  PubMed  Google Scholar 

  • Szafer, E., Pick, E., Rotman, M., Zuck, S., Huber, I., and Cassel, D. (2000). Role of coatomer and phospholipids in GTPase-activating protein-dependent hydrolysis of GTP by ADP-ribosylation factor-1. J. Biol. Chem., 275, 23615–23619.

    Article  CAS  PubMed  Google Scholar 

  • Tumbarello, D. A., Brown, M. C., and Turner, C. E. (2002). The paxillin LD motifs. FEBS Lett., 513, 114–118.

    Article  CAS  PubMed  Google Scholar 

  • Turner, C. E., Brown, M. C., Perrotta, J. A., Riedy, M. C., Nikolopoulos, S. N., McDonald, A. R., Bagrodia, S., Thomas, S., and Leventhal, P. S. (1999). Paxillin LD4 motif binds PAK and PIX through a novel 95-kD ankyrin repeat, ARF-GAP protein. J. Cell Biol., 145, 851–863.

    Article  CAS  PubMed  Google Scholar 

  • Turner, C. E., West, K. A., and Brown, M. C. (2001). Paxillin-ARF GAP signaling and the cytoskeleton. Current Opin. Cell Biol., 13, 593–599.

    CAS  Google Scholar 

  • Vitale, N., Patton, W. A., Moss, J., Vaughan, M., Lefkowitz, R. J., and Premont, R. T. (2000). GIT proteins, a novel family of phosphatidylinositol 3,4,5-trisphosphate-stimulated GTPase-activating proteins for ARF6. J. Biol. Chem., 275, 13901–13906.

    CAS  PubMed  Google Scholar 

  • Webb, D. J., Parsons, J. T., and Horwitz, A. F. (2002). Adhesion assembly, disassembly and turnover in migrating cells — over and over and over again. Nature Cell Biol., 4, E97–100.

    Article  CAS  PubMed  Google Scholar 

  • West, K. A., Zhang, H., Brown, M. C., Nikolopoulos, S. N., Riedy, M. C., Horwitz, A. R., and Turner, C. E. (2001). The LD4 motif of paxillin regulates cell spreading and motility through interaction with paxillin kinase linker. J. Cell Biol., 154, 161–176.

    Article  CAS  PubMed  Google Scholar 

  • Yoshii, S., Tanaka, M., Otsuki, Y., Wang, D.-Y., Guo, R.-J., Zhu, Y., Takeda, R., Hanai, H., Kaneko, E., and Sugimura, H. (1999). αPIX nucleotide exchange factor is activated by interaction with phosphatidylinositol 3-kinase. Oncogene, 18, 5680–5690.

    Article  CAS  PubMed  Google Scholar 

  • Zhao, Z.-S., Manser, E., Chen, X.-Q., Chong, C., Leung, T., and Lim, L. (1998) A conserved negative regulatory region in αPAK. Mol. Cell. Biol., 18, 2153–2163.

    CAS  PubMed  Google Scholar 

  • Zhao, Z.-S., Manser, E., and Lim, L. (2000a) Interaction between PAK and Nck. Mol. Cell. Biol., 20, 3906–3917.

    CAS  PubMed  Google Scholar 

  • Zhao, Z.-S., Manser, E., Loo, T.-H., and Lim, L. (2000b). Coupling of PAK-interacting exchange factor PIX to GIT1 promotes focal complex disassembly. Mol. Cell. Biol., 20, 6354–6363.

    CAS  PubMed  Google Scholar 

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  1. Department of Medicine (Gastroenterology), Duke University Medical Center, Durham, USA

    Robert Schmalzigaug & Richard Premont

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  1. Robert Schmalzigaug
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  2. Richard Premont
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Schmalzigaug, R., Premont, R. (2004). GIT Proteins: Arf Gaps and Signaling Scaffolds. In: ARF Family GTPases. Proteins and Cell Regulation, vol 1. Springer, Dordrecht. https://doi.org/10.1007/1-4020-2593-9_8

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  • DOI: https://doi.org/10.1007/1-4020-2593-9_8

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-1-4020-1719-3

  • Online ISBN: 978-1-4020-2593-8

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