Wikipedia

RAC1

Rac1, poznat i kao Ras-srodni C3 supstrat botulinum toksina 1, je protein koji se nalazi u ljudskim ćelijama. Kodiran je genom RAC1.[5][6] Ovaj gen može proizvesti razne alternativna prerade verzija proteina Rac1, za koje se čini da imaju različite funkcije.[7]

RAC1
Dostupne strukture
PDBPretraga ortologa: PDBe RCSB
Spisak PDB ID kodova

1E96, 1FOE, 1G4U, 1HE1, 1HH4, 1I4D, 1I4L, 1I4T, 1MH1, 1RYF, 1RYH, 2FJU, 2H7V, 2NZ8, 2P2L, 2RMK, 2VRW, 2WKP, 2WKQ, 2WKR, 2YIN, 3B13, 3BJI, 3RYT, 3SBD, 3SBE, 3SU8, 3SUA, 3TH5, 4GZL, 4GZM, 4YON, 5FI0

Identifikatori
AliasiRAC1
Vanjski ID-jeviOMIM: 602048 MGI: 97845 HomoloGene: 69035 GeneCards: RAC1
Lokacija gena (čovjek)
Hromosom 7 (čovjek)
Hrom.Hromosom 7 (čovjek)[1]
Hromosom 7 (čovjek)
Genomska lokacija za RAC1
Genomska lokacija za RAC1
Bend7p22.1Početak6,374,527 bp[1]
Kraj6,403,967 bp[1]
Lokacija gena (miš)
Hromosom 5 (miš)
Hrom.Hromosom 5 (miš)[2]
Hromosom 5 (miš)
Genomska lokacija za RAC1
Genomska lokacija za RAC1
Bend5 G2|5 82.22 cMPočetak143,489,389 bp[2]
Kraj143,513,791 bp[2]
Obrazac RNK ekspresije


Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija• histone deacetylase binding
• Rho GDP-dissociation inhibitor binding
• GTP-dependent protein binding
• GO:0006184 GTPase activity
• vezivanje enzima
• GO:0001948, GO:0016582 vezivanje za proteine
• thioesterase binding
• protein kinase binding
• nucleotide binding
• GTP binding
• protein serine/threonine kinase activity
• GO:0032403 protein-containing complex binding
• phosphatidylinositol-4,5-bisphosphate 3-kinase activity
• ATPase binding
Ćelijska komponenta• citoplazma
• citosol
• membrana
• focal adhesion
• Melanosom
• ruffle membrane
• trans-Golđijeva mreža
• jedro
• projekcija ćelije
• extrinsic component of plasma membrane
• Egzosom
• lamellipodium
• early endosome membrane
• ćelijska membrana
• Mikronit
• cytoplasmic ribonucleoprotein granule
• endoplasmic reticulum membrane
• Golđijeva membrana
• phagocytic cup
• GO:0016023 citoplazmatska vezikula
• GO:0005578 Vanćelijski matriks
• secretory granule membrane
• dendritična kičma
• recycling endosome membrane
• postsynapse
• glutamatergic synapse
• ficolin-1-rich granule membrane
Biološki proces• positive regulation of Rho protein signal transduction
• regulation of respiratory burst
• non-canonical Wnt signaling pathway
• positive regulation of protein phosphorylation
• positive regulation of actin filament polymerization
• regulation of neuron maturation
• negative regulation of receptor-mediated endocytosis
• platelet activation
• Fc-epsilon receptor signaling pathway
• cellular response to mechanical stimulus
• phagocytosis, engulfment
• vascular endothelial growth factor receptor signaling pathway
• substrate adhesion-dependent cell spreading
• Ćelijska proliferacija
• ruffle assembly
• lamellipodium assembly
• dopaminergic neuron differentiation
• cell-cell junction organization
• Fc-gamma receptor signaling pathway involved in phagocytosis
• ruffle organization
• actin filament organization
• cell motility
• anatomical structure morphogenesis
• bone resorption
• response to wounding
• protein localization to plasma membrane
• inflammatory response
• regulation of small GTPase mediated signal transduction
• positive regulation of cell-substrate adhesion
• G protein-coupled receptor signaling pathway
• neuron projection morphogenesis
• epithelial cell morphogenesis
• dendrite morphogenesis
• regulation of hydrogen peroxide metabolic process
• engulfment of apoptotic cell
• dendrite development
• auditory receptor cell morphogenesis
• hyperosmotic response
• cerebral cortex GABAergic interneuron development
• Hemotaksija
• positive regulation of DNA replication
• actin filament polymerization
• Ćelijska adhezija
• negative regulation of interleukin-23 production
• homeostasis of number of cells within a tissue
• cell-matrix adhesion
• localization within membrane
• actin cytoskeleton organization
• regulation of cell size
• anatomical structure arrangement
• GO:0007243 intracellular signal transduction
• regulation of cell migration
• Endocitoza
• ephrin receptor signaling pathway
• T cell costimulation
• Koagulacija (krv)
• GO:0019049, GO:0030683 mitigation of host defenses by virus
• synaptic transmission, GABAergic
• mast cell chemotaxis
• positive regulation of phosphatidylinositol 3-kinase activity
• positive regulation of substrate adhesion-dependent cell spreading
• embryonic olfactory bulb interneuron precursor migration
• cytoskeleton organization
• cochlea morphogenesis
• positive regulation of neutrophil chemotaxis
• positive regulation of apoptotic process
• regulation of cell morphogenesis
• positive regulation of focal adhesion assembly
• regulation of fibroblast migration
• positive regulation of lamellipodium assembly
• cerebral cortex radially oriented cell migration
• Ćelijska migracija
• semaphorin-plexin signaling pathway
• positive regulation of stress fiber assembly
• axon guidance
• small GTPase mediated signal transduction
• GO:0032320, GO:0032321, GO:0032855, GO:0043089, GO:0032854 positive regulation of GTPase activity
• Wnt signaling pathway, planar cell polarity pathway
• midbrain dopaminergic neuron differentiation
• neuron migration
• protein phosphorylation
• Rho protein signal transduction
• regulation of lamellipodium assembly
• Rac protein signal transduction
• cell projection assembly
• positive regulation of microtubule polymerization
• neutrophil degranulation
• regulation of nitric oxide biosynthetic process
• phosphatidylinositol phosphate biosynthetic process
• hepatocyte growth factor receptor signaling pathway
• regulation of stress fiber assembly
• positive regulation of protein kinase B signaling
• motor neuron axon guidance
• regulation of neutrophil migration
• positive regulation of insulin secretion involved in cellular response to glucose stimulus
Izvori:Amigo / QuickGO
Ortolozi
VrsteČovjekMiš
Entrez

5879

19353

Ensembl

ENSG00000136238

ENSMUSG00000001847

UniProt

P63000

P63001

RefSeq (mRNK)

NM_198829
NM_006908
NM_018890

NM_009007
NM_001347530

RefSeq (bjelančevina)

NP_008839
NP_061485

NP_001334459
NP_033033

Lokacija (UCSC)Chr 7: 6.37 – 6.4 MbChr 5: 143.49 – 143.51 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

Funkcija

uredi

Rac1 je mal (~ 21 kDa) signalizirajući G protein (tačnije GTPaza) i član je potporodice Rac porodice porodice Rho GTPaza. Članovi ove superporodice reguliraju raznolik niz ćelijskih događaja, uključujući kontrolu GLUT4,[8][9] translokaciju do unosa glukoze, rast ćelija, reorganizaciju citoskeleta, antimikrobnu citotoksičnost,[10] i aktivaciju protein kinaza.[11]

Rac1 je plejotropni regulator mnogih ćelijskih procesa, uključujući ćelijski ciklus, adheziju ćelijskih ćelija, pokretljivost (kroz aktinsku mrežu) i epitelnu diferencijaciju (predloženo da je neophodan za održavanje epidermnih matičnih ćelija).

Uloga u kanceru

uredi

Zajedno s drugom potporodicama, Rac i Rho proteina, imaj važnu regulatornu ulogu, posebno u pokretljivosti i rastu ćelija. Rac1 ima sveprisutnu tkivnu ekspresiju i podstiče pokretljivost ćelija stvaranjem lamelipodija.[12] Da bi ćlije raka mogle rasti i napadati lokalna i udaljena tkiva, deregulacija pokretljivosti ćelija jedan je od glavnih događaja u invaziji i [metastaza|[metastaziranju]] ćelija karcinoma.[13] Prekomjerna ekspresija konstitucijski aktivnog Rac1 V12 kod miševa uzrokovala je tumor koji se fenotipski ne razlikuje od ljudsog Kaposijevog sarkoma.[14] Pokazalo se da aktivacijske ili dobitne funkcije mutacije Rac1 imaju aktivnu ulogu u promociji mezenhimskog tipa kretanja ćelija, potpomognutog proteinskim kompleksima NEDD9 i DOCK3.[15] Takva abnormalna pokretljivost ćelija može rezultirati tranzicijom epitelnog mezenhima (EMT) – pokretačkim mehanizmom za metastaziranje tumora, kao i relapse tumora rezistentnog na lijekove.[16][17]

Uloga u transportu glukoze

uredi

Rac1 se ispoljava u značajnim količinama u tkivima osjetljivim na insulin, kau što su masno tkivo i skeletni mišići. Ovdje Rac1 regulira translokaciju prijenosnika glukoze GLUT4 iz unutarćelijskih odjeljaka u plazmamembranu.[9][18][19] U odgovoru na insulin, ovo omogućava ulazak glukoze u krv u ćeliji, radi smanjenja glukoze u krvi. U uvjetima gojaznosti i dijabetesa tipa 2, signalizacija Rac1 u skeletnim mišićima je disfunkcionalna, što sugerira da Rac1 doprinosi napredovanju bolesti.

Protein Rac1 je također neophodan za unos glukoze u skeletne mišiće aktivirane vježbanjem[8][20] i istezanjem.[21]

Klinički značaj

uredi

Aktivirajuće mutacije u Rac1 nedavno su otkrivene u velikim genomskim studijama koje uključuju melanom[22][23][24] i plućni karcinom malih ćelija.[25] Kao rezultat toga, Rac1 se smatra terapijskom metom za mnoge od ovih bolesti.[26]

Nekoliko nedavnih studija također je koristilo ciljanu terapiju za suzbijanje rasta tumora, farmakoinhibicijom aktivnosti Rac1 u metastatskom melanomu i karcinomu jetre, kao i u ljudskom [[Rak dojke|karcinomu dojke.[27][28][29]

Naprimjer, inhibicija puta ovisnog o Rac1 rezultirala je preokretom fenotipa tumorskih ćelija, što sugerira Rac1 kao prediktivni marker i terapijski cilj za rak dojke otporan na trastuzumab. Međutim, s obzirom na ulogu Rac1 u transportu glukoze , lijekovi koji inhibiraju Rac1 mogli bi biti štetni za homeostazu glukoze.

Dominantno negativan ili konstitutivno aktivno, klicne linije mutacije RAC1 uzrokuju različite fenotipove, koji su grupirani kao mentalna retardacija Tip 48.[30] Većina mutacija uzrokuje mikrocefaliju, dok neke specifične promjene rezultiraju makrocefalijom.

Interakcije

uredi

Pokazalo se da RAC1 ima interakcije sa:

Reference

uredi
  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000136238 - Ensembl, maj 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000001847 - Ensembl, maj 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Didsbury J, Weber RF, Bokoch GM, Evans T, Snyderman R (Oct 1989). "rac, a novel ras-related family of proteins that are botulinum toxin substrates". The Journal of Biological Chemistry. 264 (28): 16378–82. PMID 2674130.
  6. ^ Jordan P, Brazåo R, Boavida MG, Gespach C, Chastre E (Nov 1999). "Cloning of a novel human Rac1b splice variant with increased expression in colorectal tumors". Oncogene. 18 (48): 6835–9. doi:10.1038/sj.onc.1203233. PMID 10597294.
  7. ^ Zhou C, Licciulli S, Avila JL, Cho M, Troutman S, Jiang P, Kossenkov AV, Showe LC, Liu Q, Vachani A, Albelda SM, Kissil JL (Feb 2013). "The Rac1 splice form Rac1b promotes K-ras-induced lung tumorigenesis". Oncogene. 32 (7): 903–9. doi:10.1038/onc.2012.99. PMC 3384754. PMID 22430205.
  8. ^ a b Sylow, Lykke; Nielsen, Ida L.; Kleinert, Maximilian; Møller, Lisbeth L. V.; Ploug, Thorkil; Schjerling, Peter; Bilan, Philip J.; Klip, Amira; Jensen, Thomas E. (9. 4. 2016). "Rac1 governs exercise-stimulated glucose uptake in skeletal muscle through regulation of GLUT4 translocation in mice". The Journal of Physiology. 594 (17): 4997–5008. doi:10.1113/JP272039. ISSN 1469-7793. PMC 5009787. PMID 27061726.
  9. ^ a b Ueda S, Kitazawa S, Ishida K, Nishikawa Y, Matsui M, Matsumoto H, Aoki T, Nozaki S, Takeda T, Tamori Y, Aiba A, Kahn CR, Kataoka T, Satoh T (Jul 2010). "Crucial role of the small GTPase Rac1 in insulin-stimulated translocation of glucose transporter 4 to the mouse skeletal muscle sarcolemma". FASEB Journal. 24 (7): 2254–61. doi:10.1096/fj.09-137380. PMC 4183928. PMID 20203090.
  10. ^ Xiang RF (Mar 2016). "Ras-related C3 Botulinum Toxin Substrate (Rac) and Src Family Kinases (SFK) Are Proximal and Essential for Phosphatidylinositol 3-Kinase (PI3K) Activation in Natural Killer (NK) Cell-mediated Direct Cytotoxicity against Cryptococcus neoformans". J Biol Chem. 291 (13): 6912–22. doi:10.1074/jbc.M115.681544. PMC 4807276. PMID 26867574.
  11. ^ Ridley AJ (Oct 2006). "Rho GTPases and actin dynamics in membrane protrusions and vesicle trafficking". Trends in Cell Biology. 16 (10): 522–9. doi:10.1016/j.tcb.2006.08.006. PMID 16949823.
  12. ^ Parri M, Chiarugi P (2010). "Rac and Rho GTPases in cancer cell motility control". Cell Communication and Signaling. 8 (23): 23. doi:10.1186/1478-811x-8-23. PMC 2941746. PMID 20822528.
  13. ^ Hanahan D, Weinberg RA (Mar 2011). "Hallmarks of cancer: the next generation". Cell. 144 (5): 646–74. doi:10.1016/j.cell.2011.02.013. PMID 21376230.
  14. ^ Ma, Qi; Cavallin, Lucas E.; Yan, Bin; Zhu, Shoukang; Duran, Elda Margarita; Wang, Huili; Hale, Laura P.; Dong, Chunming; Cesarman, Ethel (26. 5. 2009). "Antitumorigenesis of antioxidants in a transgenic Rac1 model of Kaposi's sarcoma". Proceedings of the National Academy of Sciences (jezik: engleski). 106 (21): 8683–8688. doi:10.1073/pnas.0812688106. ISSN 0027-8424. PMC 2679580. PMID 19429708.
  15. ^ Sanz-Moreno V, Gadea G, Ahn J, Paterson H, Marra P, Pinner S, Sahai E, Marshall CJ (Oct 2008). "Rac activation and inactivation control plasticity of tumor cell movement". Cell. 135 (3): 510–23. doi:10.1016/j.cell.2008.09.043. PMID 18984162.
  16. ^ Stallings-Mann ML, Waldmann J, Zhang Y, Miller E, Gauthier ML, Visscher DW, et al. (Jul 11, 2012). "Matrix metalloproteinase induction of Rac1b, a key effector of lung cancer progression". Science Translational Medicine. 4 (142): 510–523. doi:10.1126/scitranslmed.3004062. PMC 3733503. PMID 22786680.
  17. ^ Yang WH, Lan HY, Huang CH, Tai SK, Tzeng CH, Kao SY, Wu KJ, Hung MC, Yang MH (Apr 2012). "RAC1 activation mediates Twist1-induced cancer cell migration". Nature Cell Biology. 14 (4): 366–74. doi:10.1038/ncb2455. PMID 22407364.
  18. ^ Sylow L, Kleinert M, Pehmøller C, Prats C, Chiu TT, Klip A, Richter EA, Jensen TE (Feb 2014). "Akt and Rac1 signaling are jointly required for insulin-stimulated glucose uptake in skeletal muscle and downregulated in insulin resistance". Cellular Signalling. 26 (2): 323–31. doi:10.1016/j.cellsig.2013.11.007. PMID 24216610.
  19. ^ Sylow L, Jensen TE, Kleinert M, Højlund K, Kiens B, Wojtaszewski J, Prats C, Schjerling P, Richter EA (Jun 2013). "Rac1 signaling is required for insulin-stimulated glucose uptake and is dysregulated in insulin-resistant murine and human skeletal muscle". Diabetes. 62 (6): 1865–75. doi:10.2337/db12-1148. PMC 3661612. PMID 23423567.
  20. ^ Sylow L, Jensen TE, Kleinert M, Mouatt JR, Maarbjerg SJ, Jeppesen J, Prats C, Chiu TT, Boguslavsky S, Klip A, Schjerling P, Richter EA (Apr 2013). "Rac1 is a novel regulator of contraction-stimulated glucose uptake in skeletal muscle". Diabetes. 62 (4): 1139–51. doi:10.2337/db12-0491. PMC 3609592. PMID 23274900.
  21. ^ Sylow L, Møller LL, Kleinert M, Richter EA, Jensen TE (Feb 2015). "Stretch-stimulated glucose transport in skeletal muscle is regulated by Rac1". The Journal of Physiology. 593 (3): 645–56. doi:10.1113/jphysiol.2014.284281. PMC 4324711. PMID 25416624.
  22. ^ Hodis E, Watson IR, Kryukov GV, Arold ST, Imielinski M, Theurillat JP, Nickerson E, Auclair D, Li L, Place C, Dicara D, Ramos AH, Lawrence MS, Cibulskis K, Sivachenko A, Voet D, Saksena G, Stransky N, Onofrio RC, Winckler W, Ardlie K, Wagle N, Wargo J, Chong K, Morton DL, Stemke-Hale K, Chen G, Noble M, Meyerson M, Ladbury JE, Davies MA, Gershenwald JE, Wagner SN, Hoon DS, Schadendorf D, Lander ES, Gabriel SB, Getz G, Garraway LA, Chin L (Jul 2012). "A landscape of driver mutations in melanoma". Cell. 150 (2): 251–63. doi:10.1016/j.cell.2012.06.024. PMC 3600117. PMID 22817889.
  23. ^ Krauthammer M, Kong Y, Ha BH, Evans P, Bacchiocchi A, McCusker JP, Cheng E, Davis MJ, Goh G, Choi M, Ariyan S, Narayan D, Dutton-Regester K, Capatana A, Holman EC, Bosenberg M, Sznol M, Kluger HM, Brash DE, Stern DF, Materin MA, Lo RS, Mane S, Ma S, Kidd KK, Hayward NK, Lifton RP, Schlessinger J, Boggon TJ, Halaban R (Sep 2012). "Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma". Nature Genetics. 44 (9): 1006–14. doi:10.1038/ng.2359. PMC 3432702. PMID 22842228.
  24. ^ Bauer NN, Chen YW, Samant RS, Shevde LA, Fodstad O (Nov 2007). "Rac1 activity regulates proliferation of aggressive metastatic melanoma". Experimental Cell Research. 313 (18): 3832–9. doi:10.1016/j.yexcr.2007.08.017. PMID 17904119.
  25. ^ Stallings-Mann ML, Waldmann J, Zhang Y, Miller E, Gauthier ML, Visscher DW, Downey GP, Radisky ES, Fields AP, Radisky DC (Jul 2012). "Matrix metalloproteinase induction of Rac1b, a key effector of lung cancer progression". Science Translational Medicine. 4 (142): 142ra95. doi:10.1126/scitranslmed.3004062. PMC 3733503. PMID 22786680.
  26. ^ McAllister SS (Jul 2012). "Got a light? Illuminating lung cancer". Science Translational Medicine. 4 (142): 142fs22. doi:10.1126/scitranslmed.3004446. PMID 22786678.
  27. ^ Chen QY, Xu LQ, Jiao DM, Yao QH, Wang YY, Hu HZ, et al. (Nov 2011). "Silencing of Rac1 modifies lung cancer cell migration, invasion and actin cytoskeleton rearrangements and enhances chemosensitivity to antitumor drugs". International Journal of Molecular Medicine. 28 (5): 769–776. doi:10.3892/ijmm.2011.775. PMID 21837360.
  28. ^ Dokmanovic M, Hirsch DS, Shen Y, Wu WJ (Jun 2009). "Rac1 contributes to trastuzumab resistance of breast cancer cells: Rac1 as a potential therapeutic target for the treatment of trastuzumab-resistant breast cancer". Molecular Cancer Therapeutics. 8 (6): 1557–69. doi:10.1158/1535-7163.mct-09-0140. PMID 19509242.
  29. ^ Liu S, Yu M, He Y, Xiao L, Wang F, Song C, Sun S, Ling C, Xu Z (Jun 2008). "Melittin prevents liver cancer cell metastasis through inhibition of the Rac1-dependent pathway". Hepatology. 47 (6): 1964–73. doi:10.1002/hep.22240. PMID 18506888.
  30. ^ Reijnders, Margot R.F.; Ansor, Nurhuda M.; Kousi, Maria; Yue, Wyatt W.; Tan, Perciliz L.; Clarkson, Katie; Clayton-Smith, Jill; Corning, Ken; Jones, Julie R.; Lam, Wayne W.K.; Mancini, Grazia M.S.; Marcelis, Carlo; Mohammed, Shehla; Pfundt, Rolph; Roifman, Maian; Cohn, Ronald; Chitayat, David; Millard, Tom H.; Katsanis, Nicholas; Brunner, Han G.; Banka, Siddharth (septembar 2017). "RAC1 Missense Mutations in Developmental Disorders with Diverse Phenotypes". The American Journal of Human Genetics. 101 (3): 466–477. doi:10.1016/j.ajhg.2017.08.007. PMC 5591022. PMID 28886345.
  31. ^ a b Shin OH, Exton JH (Aug 2001). "Differential binding of arfaptin 2/POR1 to ADP-ribosylation factors and Rac1". Biochemical and Biophysical Research Communications. 285 (5): 1267–73. doi:10.1006/bbrc.2001.5330. PMID 11478794.
  32. ^ Van Aelst L, Joneson T, Bar-Sagi D (Aug 1996). "Identification of a novel Rac1-interacting protein involved in membrane ruffling". The EMBO Journal. 15 (15): 3778–86. doi:10.1002/j.1460-2075.1996.tb00751.x. PMC 452058. PMID 8670882.
  33. ^ Tarricone C, Xiao B, Justin N, Walker PA, Rittinger K, Gamblin SJ, Smerdon SJ (maj 2001). "The structural basis of Arfaptin-mediated cross-talk between Rac and Arf signalling pathways". Nature. 411 (6834): 215–9. doi:10.1038/35075620. PMID 11346801.
  34. ^ Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.
  35. ^ Grizot S, Fauré J, Fieschi F, Vignais PV, Dagher MC, Pebay-Peyroula E (Aug 2001). "Crystal structure of the Rac1-RhoGDI complex involved in nadph oxidase activation". Biochemistry. 40 (34): 10007–13. doi:10.1021/bi010288k. PMID 11513578.
  36. ^ Lian LY, Barsukov I, Golovanov AP, Hawkins DI, Badii R, Sze KH, Keep NH, Bokoch GM, Roberts GC (Jan 2000). "Mapping the binding site for the GTP-binding protein Rac-1 on its inhibitor RhoGDI-1". Structure. 8 (1): 47–55. doi:10.1016/S0969-2126(00)00080-0. PMID 10673424.
  37. ^ Gorvel JP, Chang TC, Boretto J, Azuma T, Chavrier P (Jan 1998). "Differential properties of D4/LyGDI versus RhoGDI: phosphorylation and rho GTPase selectivity". FEBS Letters. 422 (2): 269–73. doi:10.1016/S0014-5793(98)00020-9. PMID 9490022.
  38. ^ Di-Poï N, Fauré J, Grizot S, Molnár G, Pick E, Dagher MC (Aug 2001). "Mechanism of NADPH oxidase activation by the Rac/Rho-GDI complex". Biochemistry. 40 (34): 10014–22. doi:10.1021/bi010289c. PMID 11513579.
  39. ^ Fauré J, Dagher MC (maj 2001). "Interactions between Rho GTPases and Rho GDP dissociation inhibitor (Rho-GDI)". Biochimie. 83 (5): 409–14. doi:10.1016/S0300-9084(01)01263-9. PMID 11368848.
  40. ^ Miki H, Yamaguchi H, Suetsugu S, Takenawa T (Dec 2000). "IRSp53 is an essential intermediate between Rac and WAVE in the regulation of membrane ruffling". Nature. 408 (6813): 732–5. doi:10.1038/35047107. PMID 11130076.
  41. ^ Westendorf JJ (Dec 2001). "The formin/diaphanous-related protein, FHOS, interacts with Rac1 and activates transcription from the serum response element". The Journal of Biological Chemistry. 276 (49): 46453–9. doi:10.1074/jbc.M105162200. PMID 11590143.
  42. ^ Yayoshi-Yamamoto S, Taniuchi I, Watanabe T (Sep 2000). "FRL, a novel formin-related protein, binds to Rac and regulates cell motility and survival of macrophages". Molecular and Cellular Biology. 20 (18): 6872–81. doi:10.1128/MCB.20.18.6872-6881.2000. PMC 86228. PMID 10958683.
  43. ^ a b Zhang B, Chernoff J, Zheng Y (Apr 1998). "Interaction of Rac1 with GTPase-activating proteins and putative effectors. A comparison with Cdc42 and RhoA". The Journal of Biological Chemistry. 273 (15): 8776–82. doi:10.1074/jbc.273.15.8776. PMID 9535855.
  44. ^ Kuroda S, Fukata M, Kobayashi K, Nakafuku M, Nomura N, Iwamatsu A, Kaibuchi K (Sep 1996). "Identification of IQGAP as a putative target for the small GTPases, Cdc42 and Rac1". The Journal of Biological Chemistry. 271 (38): 23363–7. doi:10.1074/jbc.271.38.23363. PMID 8798539.
  45. ^ Fukata M, Watanabe T, Noritake J, Nakagawa M, Yamaga M, Kuroda S, Matsuura Y, Iwamatsu A, Perez F, Kaibuchi K (Jun 2002). "Rac1 and Cdc42 capture microtubules through IQGAP1 and CLIP-170". Cell. 109 (7): 873–85. doi:10.1016/S0092-8674(02)00800-0. PMID 12110184.
  46. ^ Hart MJ, Callow MG, Souza B, Polakis P (Jun 1996). "IQGAP1, a calmodulin-binding protein with a rasGAP-related domain, is a potential effector for cdc42Hs". The EMBO Journal. 15 (12): 2997–3005. doi:10.1002/j.1460-2075.1996.tb00663.x. PMC 450241. PMID 8670801.
  47. ^ Brill S, Li S, Lyman CW, Church DM, Wasmuth JJ, Weissbach L, Bernards A, Snijders AJ (Sep 1996). "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. 16 (9): 4869–78. doi:10.1128/mcb.16.9.4869. PMC 231489. PMID 8756646.
  48. ^ Jefferies C, Bowie A, Brady G, Cooke EL, Li X, O'Neill LA (Jul 2001). "Transactivation by the p65 subunit of NF-kappaB in response to interleukin-1 (IL-1) involves MyD88, IL-1 receptor-associated kinase 1, TRAF-6, and Rac1" (PDF). Molecular and Cellular Biology. 21 (14): 4544–52. doi:10.1128/MCB.21.14.4544-4552.2001. PMC 87113. PMID 11416133.
  49. ^ Shimizu M, Wang W, Walch ET, Dunne PW, Epstein HF (Jun 2000). "Rac-1 and Raf-1 kinases, components of distinct signaling pathways, activate myotonic dystrophy protein kinase". FEBS Letters. 475 (3): 273–7. doi:10.1016/S0014-5793(00)01692-6. PMID 10869570.
  50. ^ Kitamura Y, Kitamura T, Sakaue H, Maeda T, Ueno H, Nishio S, Ohno S, Osada S, Sakaue M, Ogawa W, Kasuga M (Mar 1997). "Interaction of Nck-associated protein 1 with activated GTP-binding protein Rac". The Biochemical Journal. 322 (3): 873–8. doi:10.1042/bj3220873. PMC 1218269. PMID 9148763.
  51. ^ Katoh H, Negishi M (Jul 2003). "RhoG activates Rac1 by direct interaction with the Dock180-binding protein Elmo". Nature. 424 (6947): 461–4. doi:10.1038/nature01817. PMID 12879077.
  52. ^ Seoh ML, Ng CH, Yong J, Lim L, Leung T (Mar 2003). "ArhGAP15, a novel human RacGAP protein with GTPase binding property". FEBS Letters. 539 (1–3): 131–7. doi:10.1016/S0014-5793(03)00213-8. PMID 12650940.
  53. ^ a b Noda Y, Takeya R, Ohno S, Naito S, Ito T, Sumimoto H (Feb 2001). "Human homologues of the Caenorhabditis elegans cell polarity protein PAR6 as an adaptor that links the small GTPases Rac and Cdc42 to atypical protein kinase C". Genes to Cells. 6 (2): 107–19. doi:10.1046/j.1365-2443.2001.00404.x. PMID 11260256.
  54. ^ Qiu RG, Abo A, Steven Martin G (Jun 2000). "A human homolog of the C. elegans polarity determinant Par-6 links Rac and Cdc42 to PKCzeta signaling and cell transformation". Current Biology. 10 (12): 697–707. doi:10.1016/S0960-9822(00)00535-2. PMID 10873802.
  55. ^ Zhao C, Ma H, Bossy-Wetzel E, Lipton SA, Zhang Z, Feng GS (Sep 2003). "GC-GAP, a Rho family GTPase-activating protein that interacts with signaling adapters Gab1 and Gab2". The Journal of Biological Chemistry. 278 (36): 34641–53. doi:10.1074/jbc.M304594200. PMID 12819203.
  56. ^ Moon SY, Zang H, Zheng Y (Feb 2003). "Characterization of a brain-specific Rho GTPase-activating protein, p200RhoGAP". The Journal of Biological Chemistry. 278 (6): 4151–9. doi:10.1074/jbc.M207789200. PMID 12454018.
  57. ^ Simon AR, Vikis HG, Stewart S, Fanburg BL, Cochran BH, Guan KL (Oct 2000). "Regulation of STAT3 by direct binding to the Rac1 GTPase". Science. 290 (5489): 144–7. doi:10.1126/science.290.5489.144. PMID 11021801.
  58. ^ Worthylake DK, Rossman KL, Sondek J (Dec 2000). "Crystal structure of Rac1 in complex with the guanine nucleotide exchange region of Tiam1". Nature. 408 (6813): 682–8. doi:10.1038/35047014. PMID 11130063.
  59. ^ Gao Y, Xing J, Streuli M, Leto TL, Zheng Y (Dec 2001). "Trp(56) of rac1 specifies interaction with a subset of guanine nucleotide exchange factors". The Journal of Biological Chemistry. 276 (50): 47530–41. doi:10.1074/jbc.M108865200. PMID 11595749.

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