ARF GTPase-activating protein GIT1 is an enzyme that in humans is encoded by the GIT1 gene .[ 5] [ 6] [ 7]
GIT1 contains an ARFGAP domain, Anykrin repeats, and a GRK-interacting domain. The Arf-GAP domain, which enables it to act as a GTPase activating protein (GAP) for the Arf family of GTPases, has been shown to be involved in phosphorylation and inhibition of the ADRB2. If synaptic localization of GIT1 is disturbed, then this is known to affect dendritic spine morphology and formation—this is thought to occur through the Rac1/PAK1/LIMK/CFL1 pathway.[ 8]
^ a b c GRCh38: Ensembl release 89: ENSG00000108262 – Ensembl , May 2017^ a b c GRCm38: Ensembl release 89: ENSMUSG00000011877 – Ensembl , May 2017^ "Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ "Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ a b Premont RT, Claing A, Vitale N, Freeman JL, Pitcher JA, Patton WA, Moss J, Vaughan M, Lefkowitz RJ (December 1998). "beta2-Adrenergic receptor regulation by GIT1, a G protein-coupled receptor kinase-associated ADP ribosylation factor GTPase-activating protein" . Proc Natl Acad Sci U S A . 95 (24): 14082–14087. Bibcode :1998PNAS...9514082P . doi :10.1073/pnas.95.24.14082 PMC 24330 PMID 9826657 . ^ a b Premont RT, Claing A, Vitale N, Perry SJ, Lefkowitz RJ (August 2000). "The GIT family of ADP-ribosylation factor GTPase-activating proteins. Functional diversity of GIT2 through alternative splicing" . J Biol Chem . 275 (29): 22373–22380. doi :10.1074/jbc.275.29.22373 PMID 10896954 . ^ "Entrez Gene: GIT1 G protein-coupled receptor kinase interactor 1" .^ Zhang H, Webb DJ, Asmussen H, Horwitz AF (2003). "Synapse formation is regulated by the signaling adaptor GIT1" . J. Cell Biol . 161 (1): 131–142. doi :10.1083/jcb.200211002 . PMC 2172873 PMID 12695502 . ^ a b c d Kim S, Ko J, Shin H, Lee JR, Lim C, Han JH, Altrock WD, Garner CC, Gundelfinger ED, Premont RT, Kaang BK, Kim E (February 2003). "The GIT family of proteins forms multimers and associates with the presynaptic cytomatrix protein Piccolo" . J. Biol. Chem . 278 (8): 6291–300. doi :10.1074/jbc.M212287200 PMID 12473661 . ^ Bagrodia S, Bailey D, Lenard Z, Hart M, Guan JL, Premont RT, Taylor SJ, Cerione RA (August 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 (32): 22393–400. doi :10.1074/jbc.274.32.22393 PMID 10428811 . ^ Haendeler J, Yin G, Hojo Y, Saito Y, Melaragno M, Yan C, Sharma VK, Heller M, Aebersold R, Berk BC (December 2003). "GIT1 mediates Src-dependent activation of phospholipase Cgamma by angiotensin II and epidermal growth factor" . J. Biol. Chem . 278 (50): 49936–44. doi :10.1074/jbc.M307317200 PMID 14523024 . ^ a b c Ko J, Kim S, Valtschanoff JG, Shin H, Lee JR, Sheng M, Premont RT, Weinberg RJ, Kim E (March 2003). "Interaction between liprin-alpha and GIT1 is required for AMPA receptor targeting" . J. Neurosci . 23 (5): 1667–77. doi :10.1523/JNEUROSCI.23-05-01667.2003 . PMC 6741975 PMID 12629171 . ^ a b Ko J, Na M, Kim S, Lee JR, Kim E (October 2003). "Interaction of the ERC family of RIM-binding proteins with the liprin-alpha family of multidomain proteins" . J. Biol. Chem . 278 (43): 42377–85. doi :10.1074/jbc.M307561200 PMID 12923177 . ^ Zhao ZS, Manser E, Loo TH, Lim L (September 2000). "Coupling of PAK-interacting exchange factor PIX to GIT1 promotes focal complex disassembly" . Mol. Cell. Biol . 20 (17): 6354–63. doi :10.1128/mcb.20.17.6354-6363.2000 . PMC 86110 PMID 10938112 .
Hoefen RJ, Berk BC (2006). "The multifunctional GIT family of proteins" . J. Cell Sci . 119 (Pt 8): 1469–1475. doi :10.1242/jcs.02925 PMID 16598076 . Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery" . Genome Res . 6 (9): 791–806. doi :10.1101/gr.6.9.791 PMID 8889548 . Zhao ZS, Manser E, Loo TH, Lim L (2000). "Coupling of PAK-interacting exchange factor PIX to GIT1 promotes focal complex disassembly" . Mol. Cell. Biol . 20 (17): 6354–6363. doi :10.1128/MCB.20.17.6354-6363.2000 . PMC 86110 PMID 10938112 . Kawachi H, Fujikawa A, Maeda N, Noda M (2001). "Identification of GIT1/Cat-1 as a substrate molecule of protein tyrosine phosphatase zeta /beta by the yeast substrate-trapping system" . Proc. Natl. Acad. Sci. U.S.A . 98 (12): 6593–6598. Bibcode :2001PNAS...98.6593K . doi :10.1073/pnas.041608698 PMC 34398 PMID 11381105 . Manabe R, Kovalenko M, Webb DJ, Horwitz AR (2002). "GIT1 functions in a motile, multi-molecular signaling complex that regulates protrusive activity and cell migration". J. Cell Sci . 115 (Pt 7): 1497–510. doi :10.1242/jcs.115.7.1497 . PMID 11896197 . Nishiya N, Shirai T, Suzuki W, Nose K (2003). "Hic-5 interacts with GIT1 with a different binding mode from paxillin". J. Biochem . 132 (2): 279–89. doi :10.1093/oxfordjournals.jbchem.a003222 . PMID 12153727 . Kim S, Ko J, Shin H, Lee JR, Lim C, Han JH, Altrock WD, Garner CC, Gundelfinger ED, Premont RT, Kaang BK, Kim E (2003). "The GIT family of proteins forms multimers and associates with the presynaptic cytomatrix protein Piccolo" . J. Biol. Chem . 278 (8): 6291–6300. doi :10.1074/jbc.M212287200 PMID 12473661 . Shin H, Wyszynski M, Huh KH, Valtschanoff JG, Lee JR, Ko J, Streuli M, Weinberg RJ, Sheng M, Kim E (2003). "Association of the kinesin motor KIF1A with the multimodular protein liprin-alpha" . J. Biol. Chem . 278 (13): 11393–11401. doi :10.1074/jbc.M211874200 PMID 12522103 . Ko J, Kim S, Valtschanoff JG, Shin H, Lee JR, Sheng M, Premont RT, Weinberg RJ, Kim E (2003). "Interaction between liprin-alpha and GIT1 is required for AMPA receptor targeting" . J. Neurosci . 23 (5): 1667–77. doi :10.1523/JNEUROSCI.23-05-01667.2003 PMC 6741975 PMID 12629171 . Ko J, Na M, Kim S, Lee JR, Kim E (2004). "Interaction of the ERC family of RIM-binding proteins with the liprin-alpha family of multidomain proteins" . J. Biol. Chem . 278 (43): 42377–42385. doi :10.1074/jbc.M307561200 PMID 12923177 . Haendeler J, Yin G, Hojo Y, Saito Y, Melaragno M, Yan C, Sharma VK, Heller M, Aebersold R, Berk BC (2004). "GIT1 mediates Src-dependent activation of phospholipase Cgamma by angiotensin II and epidermal growth factor" . J. Biol. Chem . 278 (50): 49936–49944. doi :10.1074/jbc.M307317200 PMID 14523024 . van Nieuw Amerongen GP, Natarajan K, Yin G, Hoefen RJ, Osawa M, Haendeler J, Ridley AJ, Fujiwara K, van Hinsbergh VW, Berk BC (2004). "GIT1 mediates thrombin signaling in endothelial cells: role in turnover of RhoA-type focal adhesions" . Circ. Res . 94 (8): 1041–1049. doi :10.1161/01.RES.0000125627.77235.0C PMID 15016733 . Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP (2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins" . Proc. Natl. Acad. Sci. U.S.A . 101 (33): 12130–12135. Bibcode :2004PNAS..10112130B . doi :10.1073/pnas.0404720101 PMC 514446 PMID 15302935 . Goehler H, Lalowski M, Stelzl U, Waelter S, Stroedicke M, Worm U, Droege A, Lindenberg KS, Knoblich M, Haenig C, Herbst M, Suopanki J, Scherzinger E, Abraham C, Bauer B, Hasenbank R, Fritzsche A, Ludewig AH, Büssow K, Buessow K, Coleman SH, Gutekunst CA, Landwehrmeyer BG , Lehrach H, Wanker EE (2004). "A protein interaction network links GIT1, an enhancer of huntingtin aggregation, to Huntington's disease" . Mol. Cell . 15 (6): 853–865. doi :10.1016/j.molcel.2004.09.016 PMID 15383276 .
