GIT1 explained

ARF GTPase-activating protein GIT1 is an enzyme that in humans is encoded by the GIT1 gene.^{[1] [2] [3]}

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.^[4]

Interactions

GIT1 has been shown to interact with:

• ARHGEF7,^[5]
• Beta adrenergic receptor kinase,
• GIT2,
• PCLO,^[6]
• PLCG1,^[7]
  • PPFIA4 PTK2,^{[6] [8]} and
• liprin-alpha-1.^{[9] [10]}

Further reading

• Hoefen RJ, Berk BC . The multifunctional GIT family of proteins . J. Cell Sci. . 119 . Pt 8 . 1469–1475 . 2006 . 16598076 . 10.1242/jcs.02925 . free .
• Bonaldo MF, Lennon G, Soares MB . Normalization and subtraction: two approaches to facilitate gene discovery . Genome Res. . 6 . 9 . 791–806 . 1997 . 8889548 . 10.1101/gr.6.9.791 . free .
• Zhao ZS, Manser E, Loo TH, Lim L . Coupling of PAK-interacting exchange factor PIX to GIT1 promotes focal complex disassembly . Mol. Cell. Biol. . 20 . 17 . 6354–6363 . 2000 . 10938112 . 86110 . 10.1128/MCB.20.17.6354-6363.2000 .
• Kawachi H, Fujikawa A, Maeda N, Noda M . 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 . 2001 . 11381105 . 34398 . 10.1073/pnas.041608698 . 2001PNAS...98.6593K . free .
• Manabe R, Kovalenko M, Webb DJ, Horwitz AR . GIT1 functions in a motile, multi-molecular signaling complex that regulates protrusive activity and cell migration . J. Cell Sci. . 115 . Pt 7 . 1497–510 . 2002 . 10.1242/jcs.115.7.1497 . 11896197 .
• Nishiya N, Shirai T, Suzuki W, Nose K . Hic-5 interacts with GIT1 with a different binding mode from paxillin . J. Biochem. . 132 . 2 . 279–89 . 2003 . 12153727 . 10.1093/oxfordjournals.jbchem.a003222 .
• Kim S, Ko J, Shin H, Lee JR, Lim C, Han JH, Altrock WD, Garner CC, Gundelfinger ED, Premont RT, Kaang BK, Kim E . The GIT family of proteins forms multimers and associates with the presynaptic cytomatrix protein Piccolo . J. Biol. Chem. . 278 . 8 . 6291–6300 . 2003 . 12473661 . 10.1074/jbc.M212287200 . free .
• Shin H, Wyszynski M, Huh KH, Valtschanoff JG, Lee JR, Ko J, Streuli M, Weinberg RJ, Sheng M, Kim E . Association of the kinesin motor KIF1A with the multimodular protein liprin-alpha . J. Biol. Chem. . 278 . 13 . 11393–11401 . 2003 . 12522103 . 10.1074/jbc.M211874200 . free .
• Ko J, Kim S, Valtschanoff JG, Shin H, Lee JR, Sheng M, Premont RT, Weinberg RJ, Kim E . Interaction between liprin-alpha and GIT1 is required for AMPA receptor targeting . J. Neurosci. . 23 . 5 . 1667–77 . 2003 . 12629171 . 10.1523/JNEUROSCI.23-05-01667.2003. 6741975 . free .
• Ko J, Na M, Kim S, Lee JR, Kim E . Interaction of the ERC family of RIM-binding proteins with the liprin-alpha family of multidomain proteins . J. Biol. Chem. . 278 . 43 . 42377–42385 . 2004 . 12923177 . 10.1074/jbc.M307561200 . free .
• Haendeler J, Yin G, Hojo Y, Saito Y, Melaragno M, Yan C, Sharma VK, Heller M, Aebersold R, Berk BC . GIT1 mediates Src-dependent activation of phospholipase Cgamma by angiotensin II and epidermal growth factor . J. Biol. Chem. . 278 . 50 . 49936–49944 . 2004 . 14523024 . 10.1074/jbc.M307317200 . free .
• van Nieuw Amerongen GP, Natarajan K, Yin G, Hoefen RJ, Osawa M, Haendeler J, Ridley AJ, Fujiwara K, van Hinsbergh VW, Berk BC . GIT1 mediates thrombin signaling in endothelial cells: role in turnover of RhoA-type focal adhesions . Circ. Res. . 94 . 8 . 1041–1049 . 2004 . 15016733 . 10.1161/01.RES.0000125627.77235.0C. free .
• Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP . Large-scale characterization of HeLa cell nuclear phosphoproteins . Proc. Natl. Acad. Sci. U.S.A. . 101 . 33 . 12130–12135 . 2004 . 15302935 . 514446 . 10.1073/pnas.0404720101 . 2004PNAS..10112130B . free .
• Bernhard Landwehrmeyer. 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 . A protein interaction network links GIT1, an enhancer of huntingtin aggregation, to Huntington's disease . Mol. Cell . 15 . 6 . 853–865 . 2004 . 15383276 . 10.1016/j.molcel.2004.09.016 . free .

External links

• GIT1 Info with links in the Cell Migration Gateway

Notes and References

1. Premont RT, Claing A, Vitale N, Freeman JL, Pitcher JA, Patton WA, Moss J, Vaughan M, Lefkowitz RJ . 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 . December 1998 . 9826657 . 24330 . 10.1073/pnas.95.24.14082 . 1998PNAS...9514082P . free .
2. Premont RT, Claing A, Vitale N, Perry SJ, Lefkowitz RJ . The GIT family of ADP-ribosylation factor GTPase-activating proteins. Functional diversity of GIT2 through alternative splicing . J Biol Chem . 275 . 29 . 22373–22380 . August 2000 . 10896954 . 10.1074/jbc.275.29.22373 . free .
3. Web site: Entrez Gene: GIT1 G protein-coupled receptor kinase interactor 1.
4. Zhang H, Webb DJ, Asmussen H, Horwitz AF . Synapse formation is regulated by the signaling adaptor GIT1 . J. Cell Biol. . 161 . 1 . 131–142 . 2003 . 12695502 . 2172873 . 10.1083/jcb.200211002 .
5. Bagrodia S, Bailey D, Lenard Z, Hart M, Guan JL, Premont RT, Taylor SJ, Cerione RA . 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 . August 1999 . 10428811 . 10.1074/jbc.274.32.22393. free .
6. Kim S, Ko J, Shin H, Lee JR, Lim C, Han JH, Altrock WD, Garner CC, Gundelfinger ED, Premont RT, Kaang BK, Kim E . The GIT family of proteins forms multimers and associates with the presynaptic cytomatrix protein Piccolo . J. Biol. Chem. . 278 . 8 . 6291–300 . February 2003 . 12473661 . 10.1074/jbc.M212287200 . free .
7. Haendeler J, Yin G, Hojo Y, Saito Y, Melaragno M, Yan C, Sharma VK, Heller M, Aebersold R, Berk BC . GIT1 mediates Src-dependent activation of phospholipase Cgamma by angiotensin II and epidermal growth factor . J. Biol. Chem. . 278 . 50 . 49936–44 . December 2003 . 14523024 . 10.1074/jbc.M307317200 . free .
8. Zhao ZS, Manser E, Loo TH, Lim L . Coupling of PAK-interacting exchange factor PIX to GIT1 promotes focal complex disassembly . Mol. Cell. Biol. . 20 . 17 . 6354–63 . September 2000 . 10938112 . 86110 . 10.1128/mcb.20.17.6354-6363.2000.
9. Ko J, Kim S, Valtschanoff JG, Shin H, Lee JR, Sheng M, Premont RT, Weinberg RJ, Kim E . Interaction between liprin-alpha and GIT1 is required for AMPA receptor targeting . J. Neurosci. . 23 . 5 . 1667–77 . March 2003 . 12629171 . 6741975 . 10.1523/JNEUROSCI.23-05-01667.2003.
10. Ko J, Na M, Kim S, Lee JR, Kim E . Interaction of the ERC family of RIM-binding proteins with the liprin-alpha family of multidomain proteins . J. Biol. Chem. . 278 . 43 . 42377–85 . October 2003 . 12923177 . 10.1074/jbc.M307561200 . free .