Reactome | RAC1 binds effectors at the plasma membrane

RAC1 binds effectors at the plasma membrane

Stable Identifier

R-HSA-9013145

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane, cytosol

ReviewStatus

5/5

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RAC1 binds effectors at the plasma membrane

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In its GTP bound active form, plasma membrane associated RAC1 binds to the following cytosolic and plasma membrane effectors:
BAIAP2 (Lewis Saravalli et al. 2013, Bagci et al. 2020)
CAV1 (Nethe et al. 2010, Bagci et al. 2020)
CDC42BPA (Schwarz et al. 2012)
CIT (Madaule et al. 1995)
CIT 3 (Di Cunto et al. 1998)
CYFIP1 (Schneck et al. 2003, Bagci et al. 2020)
FMNL1 (Yayoshi Yamamoto et al. 2000)
IQGAP1 (Kuroda et al. 1996, Pelikan Conchaudron et al. 2011)
IQGAP2 (Brill et al. 1996, Ozdemir et al. 2018)
IQGAP3 (Wang et al. 2007)
KIAA0355 (Bagci et al. 2020: interaction studied in detail)
NISCH (Reddig et al. 2005)
NOX1 complex (Cheng et al. 2006, Miyano et al. 2006, Kao et al. 2008)
NOX2 complex (Price et al. 2002)
NOX3 complex (Ueyama et al. 2006, Miyano and Sumimoto 2007, Kao et al. 2008)
PAK1 (Parrini et al. 2002)
PAK2 (Manser et al. 1994, Manser et al. 1995, Bagci et al. 2020)
PAK3 (Manser et al. 1995)
PAK4 (Abo et al. 1998, Bagci et al. 2020)
PAK5 (Dan et al. 2002)
PAK6 (Lee et al. 2002)
PARD6A (Qiu et al. 2000)
PI3K alpha (Bokoch et at al. 1996, Murga et al. 2002)
PKN1 (Owen et al. 2003, Modha et al. 2008)
PKN2 (Zong et al. 1999)
PLD1 (Hammond et al. 1997)
PLD2 (Hiroyama and Exton 2005)
WAVE complex (Miki et al. 1998, Suetsugu et al. 2006, Bagci et al. 2020)

The following RAC1 effectors are annotated as candidate effectors either because of opposing finding reported in different studies or because they have only been reported in the high throughput screen by Bagci et al. 2020:
ABI1 (Bagci et al. 2020)
ABL2 (Bagci et al. 2020)
AMIGO2 (Bagci et al. 2020)
ARAP2 (Bagci et al. 2020)
BAIAP2L1 (Bagci et al. 2020)
BRK1 (Bagci et al. 2020)
CDC42 (Bagci et al. 2020)
CDC42EP1 (Bagci et al. 2020: binding to activated RAC1; Joberty et al. 1999: no binding to activated RAC1)
CDC42EP4 (Bagci et al. 2020: binding to activated RAC1; Joberty et al. 1999: no binding to activated RAC1)
DEPDC1B (Bagci et al. 2020)
DIAPH3 (Bagci et al. 2020)
EPHA2 (Bagci et al. 2020)
ERBIN (Bagci et al. 2020)
FERMT2 (Bagci et al. 2020)
GIT1 (Bagci et al. 2020)
GIT2 (Bagci et al. 2020)
ITGB1 (Bagci et al. 2020)
JAG1 (Bagci et al. 2020)
LAMTOR1 (Bagci et al. 2020)
MCAM (Bagci et al. 2020)
MPP7 (Bagci et al. 2020)
NCKAP1 (Bagci et al. 2020)
NHS (Bagci et al. 2020)
PLEKHG3 (Bagci et al. 2020)
PLEKHG4 (Bagci et al. 2020)
RAB7A (Bagci et al. 2020)
SLC1A5 (Bagci et al. 2020)
SNAP23 (Bagci et al. 2020)
SWAP70 (Bagci et al. 2020)
TAOK3 (Bagci et al. 2020)
TFRC (Bagci et al. 2020)
TMPO (Bagci et al. 2020)
VAMP3 (Bagci et al. 2020)
VANGL1 (Bagci et al. 2020)
WIP WASP complex (WAS, also known as WASP, a component of the WIP WASP complex, was reported to interact with active RAC1 by Aspenstrom et al. 1996 and Vastrik et al. 1999, but no interaction has been reported between RAC1 and WIP components of the complex, WIPF1, WIPF2 or WIPF3)

Active RAC1 does not bind the following RHO GTPase effectors:
ANKLE2 (Bagci et al. 2020)
ARFGAP3 (Bagci et al. 2020)
ARMCX3 (Bagci et al. 2020)
CDC42EP2 (Joberty et al. 1999)
CDC42EP3 (Joberty et al. 1999)
CDC42EP5 (Joberty et al. 1999)
DSG2 (Bagci et al. 2020)
DIAPH1 (Higashi et al. 2008)
DOCK1 (Bagci et al. 2020)
DOCK5 (Bagci et al. 2020)
ELMO2 (Bagci et al. 2020)
FMNL2 (Block et al. 2012)
HSPE1 (Bagci et al. 2020)
IL32 (Bagci et al. 2020)
LETM1 (Bagci et al. 2020)
LMAN1 (Bagci et al. 2020)
NDUFA5 (Bagci et al. 2020)
NDUFS3 (Bagci et al. 2020)
PGRMC2 (Bagci et al. 2020)
RAPGEF1 (Bagci et al. 2020)
ROCK1 (Leung et al. 1996)
ROCK2 (Leung et al. 1996)
RTKN (Reid et al. 1996)
SHMT2 (Bagci et al. 2020)
SLK (Yamada et al. 2000)
SLITRK3 (Bagci et al. 2020)
SLITRK5 (Bagci et al. 2020)
STBD1 (Bagci et al. 2020)
STX5 (Bagci et al. 2020)
VAPB (Bagci et al. 2020)

Literature References

PubMed ID	Title	Journal	Year
10873802	A human homolog of the C. elegans polarity determinant Par-6 links Rac and Cdc42 to PKCzeta signaling and cell transformation Qiu, RG, Abo, A, Steven Martin, G	Curr. Biol.	2000
16636067	Nox1-dependent reactive oxygen generation is regulated by Rac1 Lambeth, JD, Diebold, BA, Hughes, Y, Cheng, G	J. Biol. Chem.	2006
7559638	Molecular cloning of a new member of the p21-Cdc42/Rac-activated kinase (PAK) family Lim, L, Michael, G, Chong, C, Manser, E, Leung, T, Zhao, ZS, Hall, C	J. Biol. Chem.	1995
18218625	Biochemical characterization of the Rho GTPase-regulated actin assembly by diaphanous-related formins, mDia1 and Daam1, in platelets Ikeda, T, Kondo, H, Horiuchi, H, Okuda, T, Okawa, K, Shirakawa, R, Higashi, T, Kita, T, Kawato, M, Nureki, O, Fukai, S, Horiguchi, M	J. Biol. Chem.	2008
10508610	Sema3A-induced growth-cone collapse is mediated by Rac1 amino acids 17-32 Ridley, A, Västrik, I, Eickholt, BJ, Doherty, P, Walsh, FS	Curr. Biol.	1999
16702231	Optimization of WAVE2 complex-induced actin polymerization by membrane-bound IRSp53, PIP(3), and Rac Takenawa, T, Yamazaki, D, Oikawa, T, Kurisu, S, Suetsugu, S, Oda, A	J Cell Biol	2006
11756552	PAK5, a new brain-specific kinase, promotes neurite outgrowth in N1E-115 cells Dan, C, Minden, A, Liberto, M, Nath, N	Mol. Cell. Biol.	2002
21730051	The IQGAP1 protein is a calmodulin-regulated barbed end capper of actin filaments: possible implications in its function in cell migration Carlier, MF, Didry, D, Pelikan-Conchaudron, A, Le Clainche, C	J. Biol. Chem.	2011
9843499	WAVE, a novel WASP-family protein involved in actin reorganization induced by Rac Miki, H, Takenawa, T, Suetsugu, S	EMBO J	1998
8816443	The p160 RhoA-binding kinase ROK alpha is a member of a kinase family and is involved in the reorganization of the cytoskeleton Lim, L, Manser, E, Leung, T, Chen, XQ	Mol. Cell. Biol.	1996
16762923	Direct involvement of the small GTPase Rac in activation of the superoxide-producing NADPH oxidase Nox1 Takeya, R, Miyano, K, Sumimoto, H, Ueno, N	J. Biol. Chem.	2006
10699464	Molecular cloning and characterization of a novel human STE20-like kinase, hSLK Kohama, Y, Itoh, S, Yamada, E, Kameda, Y, Yamamoto, H, Tsujikawa, K	Biochim. Biophys. Acta	2000
11896053	Rac activation induces NADPH oxidase activity in transgenic COSphox cells, and the level of superoxide production is exchange factor-dependent Atkinson, SJ, Price, MO, Dinauer, MC, Knaus, UG	J Biol Chem	2002
23707487	ARF1 controls Rac1 signaling to regulate migration of MDA-MB-231 invasive breast cancer cells Claing, A, Lewis-Saravalli, S, Campbell, S	Cell. Signal.	2013
17583407	Role of the small GTPase Rac in p22phox-dependent NADPH oxidases Miyano, K, Sumimoto, H	Biochimie	2007
10958683	FRL, a novel formin-related protein, binds to Rac and regulates cell motility and survival of macrophages Yayoshi-Yamamoto, S, Taniuchi, I, Watanabe, T	Mol. Cell. Biol.	2000
18347018	Identification of a conserved Rac-binding site on NADPH oxidases supports a direct GTPase regulatory mechanism Bohl, B, Taylor, RM, Gianni, D, Bokoch, GM, Kao, YY	J. Biol. Chem.	2008
16002401	Regulation of p21-activated kinase-independent Rac1 signal transduction by nischarin Juliano, RL, Reddig, PJ, Xu, D	J. Biol. Chem.	2005
8662891	Rhotekin, a new putative target for Rho bearing homology to a serine/threonine kinase, PKN, and rhophilin in the rho-binding domain Madaule, P, Fujisawa, K, Narumiya, S, Furuyashiki, T, Watanabe, G, Reid, T, Watanabe, N, Ishizaki, T, Morii, N	J. Biol. Chem.	1996
22608513	FMNL2 drives actin-based protrusion and migration downstream of Cdc42 Kühn, S, Rottner, K, Kage, F, Duwe, P, Stradal, TE, Rohn, JL, Faix, J, Baum, B, Breitsprecher, D, Geffers, R, Winterhoff, M, Geyer, M, Block, J, Brakebusch, C	Curr. Biol.	2012
8798539	Identification of IQGAP as a putative target for the small GTPases, Cdc42 and Rac1 Kobayashi, K, Kaibuchi, K, Fukata, M, Kuroda, S, Nakafuku, M, Nomura, N, Iwamatsu, A	J. Biol. Chem.	1996
22970203	Serine-71 phosphorylation of Rac1 modulates downstream signaling Hävemeier, A, Proff, J, Just, I, Schwarz, J, Barlag, B, Rottner, K, Gerhard, R, Pich, A, Tatge, H, Ladwein, M	PLoS ONE	2012
11773441	AR and ER interaction with a p21-activated kinase (PAK6) Balk, SP, Lu, ML, Lee, SR, Masiello, D, Ramos, SM, Swanson, KD, Ko, A	Mol. Endocrinol.	2002
8805223	Two GTPases, Cdc42 and Rac, bind directly to a protein implicated in the immunodeficiency disorder Wiskott-Aldrich syndrome Lindberg, U, Hall, A, Aspenström, P	Curr Biol	1996
11803464	Rac1 and RhoG promote cell survival by the activation of PI3K and Akt, independently of their ability to stimulate JNK and NF-kappaB Murga, C, Teramoto, H, Zohar, M, Gutkind, JS	Oncogene	2002
10490598	The Borgs, a new family of Cdc42 and TC10 GTPase-interacting proteins Joberty, G, Macara, IG, Perlungher, RR	Mol. Cell. Biol.	1999
8107774	A brain serine/threonine protein kinase activated by Cdc42 and Rac1 Manser, E, Leung, T, Lim, L, Zhao, ZS, Salihuddin, H	Nature	1994
18006505	The Rac1 polybasic region is required for interaction with its effector PRK1 Mott, HR, Campbell, LJ, Owen, D, Nietlispach, D, Buhecha, HR, Modha, R	J. Biol. Chem.	2008
31871319	Mapping the proximity interaction network of the Rho-family GTPases reveals signalling pathways and regulatory mechanisms Tran, V, Gingras, AC, Elkholi, IE, Robert, A, Boulais, J, Faubert, D, Dubé, N, Hipfner, DR, Cote, JF, Lin, ZY, Bagci, H, Sriskandarajah, N, Thibault, MP	Nat. Cell Biol.	2020
9988689	Loop 6 of RhoA confers specificity for effector binding, stress fiber formation, and cellular transformation Raman, N, Quilliam, LA, Atkinson, SJ, Mickelson-Young, LA, Zong, H	J. Biol. Chem.	1999
8645157	Rac GTPase interacts specifically with phosphatidylinositol 3-kinase Knaus, UG, Wang, Y, Bokoch, GM, Traynor-Kaplan, AE, Vlahos, CJ	Biochem J	1996
29358323	Unraveling the molecular mechanism of interactions of the Rho GTPases Cdc42 and Rac1 with the scaffolding protein IQGAP2 Nussinov, R, Ozdemir, ES, Jang, H, Keskin, O, Sacks, DB, Li, Z, Gursoy, A	J. Biol. Chem.	2018
9792683	Citron rho-interacting kinase, a novel tissue-specific ser/thr kinase encompassing the Rho-Rac-binding protein Citron Calautti, E, Turco, E, Di Cunto, F, Ong, L, Dotto, GP, Topley, G, Hsiao, J	J. Biol. Chem.	1998
16507994	Involvement of Rac1 in activation of multicomponent Nox1- and Nox3-based NADPH oxidases Geiszt, M, Ueyama, T, Leto, TL	Mol. Cell. Biol.	2006
17244649	IQGAP3, a novel effector of Rac1 and Cdc42, regulates neurite outgrowth Kaibuchi, K, Arimura, N, Fukata, M, Yoshimura, T, Noritake, J, Nakagawa, M, Matsuura, Y, Itoh, N, Watanabe, T, Wang, S, Harada, T	J. Cell. Sci.	2007
14514689	Molecular dissection of the interaction between the small G proteins Rac1 and RhoA and protein kinase C-related kinase 1 (PRK1) Mott, HR, Owen, D, Chirgadze, DY, Nietlispach, D, Brosnan, CE, Parker, PJ, Lowe, PN, Blundell, TL	J. Biol. Chem.	2003
9822598	PAK4, a novel effector for Cdc42Hs, is implicated in the reorganization of the actin cytoskeleton and in the formation of filopodia Dan, C, Belisle, B, Qu, J, Baud, V, Abo, A, Minden, A, Fritsch, A, Cammarano, MS	EMBO J.	1998
11804587	Pak1 kinase homodimers are autoinhibited in trans and dissociated upon activation by Cdc42 and Rac1 Parrini, MC, Lei, M, Mayer, BJ, Harrison, SC	Mol Cell	2002
20460433	Focal-adhesion targeting links caveolin-1 to a Rac1-degradation pathway Deelder, AM, Anthony, EC, Hensbergen, PJ, Fernandez-Borja, M, Hordijk, PL, Dee, R, Geerts, D, Nethe, M, Schmidt, G	J. Cell. Sci.	2010
8543060	A novel partner for the GTP-bound forms of rho and rac Madaule, P, Narumiya, S, Furuyashiki, T, Watanabe, G, Reid, T, Ishizaki, T, Morii, N	FEBS Lett.	1995
9013646	Characterization of two alternately spliced forms of phospholipase D1. Activation of the purified enzymes by phosphatidylinositol 4,5-bisphosphate, ADP-ribosylation factor, and Rho family monomeric GTP-binding proteins and protein kinase C-alpha Morris, AJ, Nozawa, Y, Frohman, MA, Cadwallader, K, Hammond, SM, Prestwich, GD, Cook, S, Gu, Q, Jenco, JM, Nakashima, S	J. Biol. Chem.	1997
8756646	The Ras GTPase-activating-protein-related human protein IQGAP2 harbors a potential actin binding domain and interacts with calmodulin and Rho family GTPases Li, S, Church, DM, Weissbach, L, Wasmuth, JJ, Lyman, CW, Snijders, AJ, Bernards, A, Brill, S	Mol. Cell. Biol.	1996