Signaling by Rho GTPases

Kalpachidou T, Spiecker L, Kress M, Quarta S. Rho GTPases in the Physiology and Pathophysiology of Peripheral Sensory Neurons. Cells. 2019 Jun 15;8(6). PMID: 31208035; PMCID: PMC6627758.; Haga RB, Ridley AJ. Rho GTPases: Regulation and roles in cancer cell biology. Small GTPases. 2016 Sep 26;7(4):207–21. doi: 10.1080/21541248.2016.1232583.; Hodge RG, Ridley AJ. Regulating Rho GTPases and their regulators. Nature Reviews Molecular Cell Biology. 2016 Jun 15;17(8):496–510. doi: 10.1038/nrm.2016.67.; Kühn S, Geyer M. Formins as effector proteins of Rho GTPases. Small GTPases. 2014;5():e29513. PMID: 24914801; PMCID: PMC4111664.; Lane J, Martin T, Weeks HP, Jiang WG. Structure and role of WASP and WAVE in Rho GTPase signalling in cancer. Cancer Genomics Proteomics. 2014 May;11(3):155–65. PMID: 24969695.; Jyoti A, Singh AK, Dubey M, Kumar S, Saluja R, Keshari RS, Verma A, Chandra T, Kumar A, Bajpai VK, Barthwal MK, Dikshit M. Interaction of inducible nitric oxide synthase with rac2 regulates reactive oxygen and nitrogen species generation in the human neutrophil phagosomes: implication in microbial killing. Antioxid Redox Signal. 2014 Jan 20;20(3):417–31. doi: 10.1089/ars.2012.4970. PMID: 23875749.; Bassi ZI, Audusseau M, Riparbelli MG, Callaini G, D'Avino PP. Citron kinase controls a molecular network required for midbody formation in cytokinesis. Proc Natl Acad Sci U S A. 2013 Jun 11;110(24):9782–7. PMID: 23716662; PMCID: PMC3683733.; Watanabe S, De Zan T, Ishizaki T, Narumiya S. Citron kinase mediates transition from constriction to abscission through its coiled-coil domain. J Cell Sci. 2013 Apr 15;126(Pt 8):1773–84. doi: 10.1242/jcs.116608. PMID: 23444367.; Pelikan-Conchaudron A, Le Clainche C, Didry D, Carlier MF. The IQGAP1 protein is a calmodulin-regulated barbed end capper of actin filaments: possible implications in its function in cell migration. J Biol Chem. 2011 Oct 07;286(40):35119–28. PMID: 21730051; PMCID: PMC3186398.; Hage B, Meinel K, Baum I, Giehl K, Menke A. Rac1 activation inhibits E-cadherin-mediated adherens junctions via binding to IQGAP1 in pancreatic carcinoma cells. Cell Communication and Signaling. 2009 Sep 08;7(1):23. doi: 10.1186/1478-811x-7-23.; Szczepanowska J. Involvement of Rac/Cdc42/PAK pathway in cytoskeletal rearrangements. Acta Biochim Pol. 2009 Jun 10;56(2). doi: 10.18388/abp.2009_2453.; Suzuki K, Takahashi K. Regulation of lamellipodia formation and cell invasion by CLIP-170 in invasive human breast cancer cells. Biochemical and Biophysical Research Communications. 2008 Apr;368(2):199–204. doi: 10.1016/j.bbrc.2008.01.069.; Metzger E, Yin N, Wissmann M, Kunowska N, Fischer K, Friedrichs N, Patnaik D, Higgins JM, Potier N, Scheidtmann KH, Buettner R, Schüle R. Phosphorylation of histone H3 at threonine 11 establishes a novel chromatin mark for transcriptional regulation. Nat Cell Biol. 2008 Jan;10(1):53–60. PMID: 18066052; PMCID: PMC2878724.; Wang S, Watanabe T, Noritake J, Fukata M, Yoshimura T, Itoh N, Harada T, Nakagawa M, Matsuura Y, Arimura N, Kaibuchi K. IQGAP3, a novel effector of Rac1 and Cdc42, regulates neurite outgrowth. J Cell Sci. 2007 Feb 15;120(Pt 4):567–77. doi: 10.1242/jcs.03356. PMID: 17244649.; Sudo K, Ito H, Iwamoto I, Morishita R, Asano T, Nagata K. Identification of a cell polarity-related protein, Lin-7B, as a binding partner for a Rho effector, Rhotekin, and their possible interaction in neurons. Neurosci Res. 2006 Dec;56(4):347–55. doi: 10.1016/j.neures.2006.08.003. PMID: 16979770.; Boureux A, Vignal E, Faure S, Fort P. Evolution of the Rho family of ras-like GTPases in eukaryotes. Mol Biol Evol. 2007 Jan;24(1):203–16. PMID: 17035353; PMCID: PMC2665304.; Miyano K, Ueno N, Takeya R, Sumimoto H. Direct Involvement of the Small GTPase Rac in Activation of the Superoxide-producing NADPH Oxidase Nox1. Journal of Biological Chemistry. 2006 Aug;281(31):21857–68. doi: 10.1074/jbc.m513665200.; Cheng G, Diebold BA, Hughes Y, Lambeth JD. Nox1-dependent Reactive Oxygen Generation Is Regulated by Rac1. Journal of Biological Chemistry. 2006 Jun;281(26):17718–26. doi: 10.1074/jbc.m512751200.; Ueyama T, Geiszt M, Leto TL. Involvement of Rac1 in Activation of Multicomponent Nox1- and Nox3-Based NADPH Oxidases. Molecular and Cellular Biology. 2006 Mar 01;26(6):2160–74. doi: 10.1128/mcb.26.6.2160-2174.2006.; Gruneberg U, Neef R, Li X, Chan EH, Chalamalasetty RB, Nigg EA, Barr FA. KIF14 and citron kinase act together to promote efficient cytokinesis. J Cell Biol. 2006 Jan 30;172(3):363–72. PMID: 16431929; PMCID: PMC2063646.; Bernards A. Ras superfamily and interacting proteins database. Methods Enzymol. 2006;407():1–9. doi: 10.1016/s0076-6879(05)07001-1. PMID: 16757309.; Jaffe AB, Hall A. Rho GTPases: biochemistry and biology. Annu Rev Cell Dev Biol. 2005;21():247–69. doi: 10.1146/annurev.cellbio.21.020604.150721. PMID: 16212495.; Metzger E, Wissmann M, Yin N, Müller JM, Schneider R, Peters AH, Günther T, Buettner R, Schüle R. LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription. Nature. 2005 Sep 15;437(7057):436–9. doi: 10.1038/nature04020. PMID: 16079795.; Govek EE, Newey SE, Van Aelst L. The role of the Rho GTPases in neuronal development. Genes Dev. 2005 Jan 01;19(1):1–49. doi: 10.1101/gad.1256405. PMID: 15630019.; Aspenström P, Fransson A, Saras J. Rho GTPases have diverse effects on the organization of the actin filament system. Biochem J. 2004 Jan 15;377(Pt 2):327–37. PMID: 14521508; PMCID: PMC1223866.; Camera P, da Silva JS, Griffiths G, Giuffrida MG, Ferrara L, Schubert V, Imarisio S, Silengo L, Dotti CG, Di Cunto F. Citron-N is a neuronal Rho-associated protein involved in Golgi organization through actin cytoskeleton regulation. Nat Cell Biol. 2003 Dec;5(12):1071–8. doi: 10.1038/ncb1064. PMID: 14595335.; Riento K, Ridley AJ. ROCKs: multifunctional kinases in cell behaviour. Nature Reviews Molecular Cell Biology. 2003 Jun 01;4(6):446–56. doi: 10.1038/nrm1128.; Miralles F, Posern G, Zaromytidou AI, Treisman R. Actin dynamics control SRF activity by regulation of its coactivator MAL. Cell. 2003 May 02;113(3):329–42. doi: 10.1016/s0092-8674(03)00278-2. PMID: 12732141.; Bernards A. GAPs galore! A survey of putative Ras superfamily GTPase activating proteins in man and Drosophila. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer. 2003 Mar;1603(2):47–82. doi: 10.1016/s0304-419x(02)00082-3.; Metzger E, Müller JM, Ferrari S, Buettner R, Schüle R. A novel inducible transactivation domain in the androgen receptor: implications for PRK in prostate cancer. EMBO J. 2003 Jan 15;22(2):270–80. PMID: 12514133; PMCID: PMC140098.; Mircescu H, Steuve S, Savonet V, Degraef C, Mellor H, Dumont JE, Maenhaut C, Pirson I. Identification and characterization of a novel activated RhoB binding protein containing a PDZ domain whose expression is specifically modulated in thyroid cells by cAMP. European Journal of Biochemistry. 2002 Dec;269(24):6241–9. doi: 10.1046/j.1432-1033.2002.03343.x.; Peck JW, Oberst M, Bouker KB, Bowden E, Burbelo PD. The RhoA-binding protein, Rhophilin-2, Regulates Actin Cytoskeleton Organization. Journal of Biological Chemistry. 2002 Nov;277(46):43924–32. doi: 10.1074/jbc.m203569200.; Schmidt A, Hall A. Guanine nucleotide exchange factors for Rho GTPases: turning on the switch. Genes Dev. 2002 Jul 01;16(13):1587–609. doi: 10.1101/gad.1003302. PMID: 12101119.; Fukata M, Watanabe T, Noritake J, Nakagawa M, Yamaga M, Kuroda S, Matsuura Y, Iwamatsu A, Perez F, Kaibuchi K. Rac1 and Cdc42 capture microtubules through IQGAP1 and CLIP-170. Cell. 2002 Jun 28;109(7):873–85. doi: 10.1016/s0092-8674(02)00800-0. PMID: 12110184.; Sahai E, Marshall CJ. RHO-GTPases and cancer. Nat Rev Cancer. 2002 Feb;2(2):133–42. doi: 10.1038/nrc725. PMID: 12635176.; Vignal E, Blangy A, Martin M, Gauthier-Rouvie`re C, Fort P. Kinectin Is a Key Effector of RhoG Microtubule-Dependent Cellular Activity. Mol Cell Biol. 2001 Dec;21(23):8022–34. doi: 10.1128/mcb.21.23.8022-8034.2001.; Kim C, Dinauer MC. Rac2 is an essential regulator of neutrophil nicotinamide adenine dinucleotide phosphate oxidase activation in response to specific signaling pathways. J Immunol. 2001 Jan 15;166(2):1223–32. doi: 10.4049/jimmunol.166.2.1223. PMID: 11145705.; Misaki K, Mukai H, Yoshinaga C, Oishi K, Isagawa T, Takahashi M, Ohsumi K, Kishimoto T, Ono Y. PKN delays mitotic timing by inhibition of Cdc25C: possible involvement of PKN in the regulation of cell division. Proc Natl Acad Sci U S A. 2001 Jan 02;98(1):125–9. PMID: 11134534; PMCID: PMC14555.; Reynaud C, Fabre S, Jalinot P. The PDZ Protein TIP-1 Interacts with the Rho Effector Rhotekin and Is Involved in Rho Signaling to the Serum Response Element. Journal of Biological Chemistry. 2000 Oct;275(43):33962–8. doi: 10.1074/jbc.m000465200.; Hamaguchi T, Ito M, Feng J, Seko T, Koyama M, Machida H, Takase K, Amano M, Kaibuchi K, Hartshorne DJ, Nakano T. Phosphorylation of CPI-17, an Inhibitor of Myosin Phosphatase, by Protein Kinase N. Biochemical and Biophysical Research Communications. 2000 Aug;274(3):825–30. doi: 10.1006/bbrc.2000.3225.; Fujita A, Nakamura K, Kato T, Watanabe N, Ishizaki T, Kimura K, Mizoguchi A, Narumiya S. Ropporin, a sperm-specific binding protein of rhophilin, that is localized in the fibrous sheath of sperm flagella. J Cell Sci. 2000 Jan;113 ( Pt 1)():103–12. doi: 10.1242/jcs.113.1.103. PMID: 10591629.; Daniels RH, Bokoch GM. p21-activated protein kinase: a crucial component of morphological signaling? Trends Biochem Sci. 1999 Sep;24(9):350–5. doi: 10.1016/s0968-0004(99)01442-5. PMID: 10470034.; Murphy GA, Solski PA, Jillian SA, Pérez de la Ossa P, D'Eustachio P, Der CJ, Rush MG. Cellular functions of TC10, a Rho family GTPase: regulation of morphology, signal transduction and cell growth. Oncogene. 1999 Jul 01;18(26):3831–45. doi: 10.1038/sj.onc.1202758. PMID: 10445846.; Roberts AW, Kim C, Zhen L, Lowe JB, Kapur R, Petryniak B, Spaetti A, Pollock JD, Borneo JB, Bradford GB, Atkinson SJ, Dinauer MC, Williams DA. Deficiency of the hematopoietic cell-specific Rho family GTPase Rac2 is characterized by abnormalities in neutrophil function and host defense. Immunity. 1999 Feb;10(2):183–96. doi: 10.1016/s1074-7613(00)80019-9. PMID: 10072071.; Takahashi M, Mukai H, Toshimori M, Miyamoto M, Ono Y. Proteolytic activation of PKN by caspase-3 or related protease during apoptosis. Proc. Natl. Acad. Sci. U.S.A. 1998 Sep 29;95(20):11566–71. doi: 10.1073/pnas.95.20.11566.; Fukata M, Kuroda S, Fujii K, Nakamura T, Shoji I, Matsuura Y, Okawa K, Iwamatsu A, Kikuchi A, Kaibuchi K. Regulation of Cross-linking of Actin Filament by IQGAP1, a Target for Cdc42. Journal of Biological Chemistry. 1997 Nov;272(47):29579–83. doi: 10.1074/jbc.272.47.29579.; Van Aelst L, D'Souza-Schorey C. Rho GTPases and signaling networks. Genes Dev. 1997 Sep 15;11(18):2295–322. doi: 10.1101/gad.11.18.2295. PMID: 9308960.; Bashour AM, Fullerton AT, Hart MJ, Bloom GS. IQGAP1, a Rac- and Cdc42-binding protein, directly binds and cross-links microfilaments. J Cell Biol. 1997 Jun 30;137(7):1555–66. PMID: 9199170; PMCID: PMC2137827.; Kuroda S, Fukata M, Kobayashi K, Nakafuku M, Nomura N, Iwamatsu A, Kaibuchi K. Identification of IQGAP as a Putative Target for the Small GTPases, Cdc42 and Rac1. Journal of Biological Chemistry. 1996 Sep;271(38):23363–7. doi: 10.1074/jbc.271.38.23363.; Brill S, Li S, Lyman CW, Church DM, Wasmuth JJ, Weissbach L, Bernards A, Snijders AJ. The Ras GTPase-Activating-Protein-Related Human Protein IQGAP2 Harbors a Potential Actin Binding Domain and Interacts with Calmodulin and Rho Family GTPases. Molecular and Cellular Biology. 1996 Sep 01;16(9):4869–78. doi: 10.1128/mcb.16.9.4869.; Hotta K, Tanaka K, Mino A, Kohno H, Takai Y. Interaction of the Rho Family Small G Proteins with Kinectin, an Anchoring Protein of Kinesin Motor. Biochemical and Biophysical Research Communications. 1996 Aug;225(1):69–74. doi: 10.1006/bbrc.1996.1132.; Watanabe G, Saito Y, Madaule P, Ishizaki T, Fujisawa K, Morii N, Mukai H, Ono Y, Kakizuka A, Narumiya S. Protein kinase N (PKN) and PKN-related protein rhophilin as targets of small GTPase Rho. Science. 1996 Feb 02;271(5249):645–8. doi: 10.1126/science.271.5249.645. PMID: 8571126.; Knaus UG, Heyworth PG, Evans T, Curnutte JT, Bokoch GM. Regulation of phagocyte oxygen radical production by the GTP-binding protein Rac 2. Science. 1991 Dec 06;254(5037):1512–5. doi: 10.1126/science.1660188. PMID: 1660188.

Metabolites

H2O

Formula: H2O (18.0105642)

CAS ID: 7732-18-5

ATP(4-)

Formula: C10H12N5O13P3 (502.9644492)

CAS ID:

GTP(4-)

Formula: C10H12N5O14P3 (518.9593642)

CAS ID: 86527-72-2

ADP(3-)

Formula: C10H12N5O10P2 (424.0059412)

CAS ID:



Enzyme

EC Number name full name note
2.7.1.137 phosphatidylinositol 3-kinase ATP:1-phosphatidyl-1D-myo-inositol 3-phosphotransferase
2.7.11.1 non-specific serine/threonine protein kinase ATP:protein phosphotransferase (non-specific)
2.7.11.24 mitogen-activated protein kinase ATP:protein phosphotransferase (MAPKK-activated)
3.1.3.48 protein-tyrosine-phosphatase protein-tyrosine-phosphate phosphohydrolase
5.2.1.8 peptidylprolyl isomerase Peptidylproline cis-trans-isomerase


Proteins

Protein ID name full name
O42900 vps15 Serine/threonine-protein kinase vps15
O74448 pin1 Peptidyl-prolyl cis-trans isomerase pin1
P06652 cdc25 M-phase inducer phosphatase
P50520 pik3 Phosphatidylinositol 3-kinase pik3
P50527 shk1 Serine/threonine-protein kinase shk1/pak1
Q09892 sty1 Mitogen-activated protein kinase sty1
Q12701 ksg1 Serine/threonine-protein kinase ksg1