Reactome | CDC42 binds effectors at the plasma membrane

CDC42 binds effectors at the plasma membrane

Stable Identifier

R-HSA-9013157

Type

Reaction

Species

Homo sapiens

Compartment

plasma membrane, cytosol

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CDC42 binds effectors at the plasma membrane

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The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

In its GTP bound active form, plasma membrane associated CDC42 binds to the following effectors:
BAIAP2 (Krugmann et al. 2001; Kast et al. 2014)
CDC42BPA (also known as MRCK alpha or MRCKA) (Leung et al. 1998; Schwarz et al. 2012; Bagci et al. 2020)
CDC42BPB (also known as MRCK beta or MRCKB) (Zihni et al. 2017; Bagci et al. 2020)
CDC42EP1 (also known as Borg5) (Joberty et al. 1999; Bagci et al. 2020)
CDC42EP2 (also known as Borg1) (Joberty et al. 1999; Bagci et al. 2020)
CDC42EP3 (also known as Borg2) (Joberty et al. 1999)
CDC42EP4 (also known as Borg4) (Joberty et al. 1999; Bagci et al. 2020)
CDC42EP5 (also known as Borg3) (Joberty et al. 1999)
FMNL1 (Kuhn et al. 2015)
FMNL2 (Block et al. 2012; Kuhn et al. 2015)
FMNL3 (Richards et al. 2015)
FNBP1 (also known as FBP17) (Chan Wah Hak et al. 2018; Bagci et al. 2020)
FNBP1L (also known as Toca-1) (Ho et al. 2004; Bagci et al. 2020)
IQGAP1 (Hart et al. 1996; Kuroda et al. 1996; Swart Mataraza et al. 2002)
IQGAP2 (Brill et al. 1996)
MAP3K11 (Leung and Lassam 1998)
PAK1 (Parrini et al. 2002; Bagci et al. 2020)
PAK2 (Wu and Wang 2003; Bagci et al. 2020)
PAK3 (Rousseau et al. 2003)
PAK5 (Dan et al. 2002; Ching et al. 2003, Wu and Frost 2006)
PAK6 (Lee et al. 2002, Morse et al. 2016)
PAK7 (Amado Azevedo et al. 2017)
PARD6A (Qiu et al. 2000)
PLD1 (Hammond et al. 1997)
WASP complex, through interaction with WASP complex components WASL (Kim et al. 2000; Bagci et al. 2020), WAS (WASP) (Aspenstrom et al. 1996), WIPF1 (also known as WIP) (Ramesh et al. 1997), WIPF2 (Bagci et al. 2020) and WIPF3 (Bagci et al. 2020)

The following putative CDC42 effectors are annotated as candidates either because of the opposing findings reported by different studies or because they have only been reported in the high throughput screen by Bagci et al. 2020 as proteins that bind to constitutively active CDC42 mutant:
ARFGAP2 (Bagci et al. 2020)
ARFGAP3 (Bagci et al. 2020)
ARHGAP1 (Bagci et al. 2020)
ARHGEF7 (Bagci et al. 2020)
CAV1 (Bagci et al. 2020)
CDC42SE2 (Bagci et al. 2020)
CPNE8 (Bagci et al. 2020)
DAAM1 (Aspenstrom et al. 2006: binding to active CDC42; Higashi et al. 2008: no binding to active CDC42)
DEPDC1B (Bagci et al. 2020)
DIAPH3 (Bagci et al. 2020)
GIT1 (Bagci et al. 2020)
GIT2 (Bagci et al. 2020)
GOLGA8R (Bagci et al. 2020)
IQGAP3 (Wang et al. 2007: binding to active CDC42; Bagci et al. 2020: no binding to active CDC42)
JUP (Bagci et al. 2020)
KCTD3 (Bagci et al. 2020)
LAMTOR1 (Bagci et al. 2020)
PAK4 (Bagci et al. 2020)
RAB7A (Bagci et al. 2020)
SCRIB (Bagci et al. 2020)
SH3PXD2A (Bagci et al. 2020)
SHKBP1 (Bagci et al. 2020)
SNAP23 (Bagci et al. 2020)
STEAP3 (Bagci et al. 2020)
STOM (Bagci et al. 2020)
TFRC (Bagci et al. 2020)
TMPO (Bagci et al. 2020)
VAMP3 (Bagci et al. 2020)
VANGL1 (Bagci et al. 2020)
WDR81 (Bagci et al. 2020)
WDR91 (Bagci et al. 2020)

CDC42 does not bind the following RHO GTPase effectors:
ARL13B (Bagci et al. 2020)
DIAPH1 (Higashi et al. 2008)
GFOD1 (Bagci et al. 2020)
GJA1 (Bagci et al. 2020)
KIAA0355 (Bagci et al. 2020)
MPP7 (Bagci et al. 2020)
NIPSNAP2 (Bagci et al. 2020)
PLEKHG3 (Bagci et al. 2020)
ROCK1 (Leung et al. 1996)
ROCK2 (Leung et al. 1996)
RTKN (Reid et al. 1996)
SLC1A5 (Bagci et al. 2020)
SLC4A7 (Bagci et al. 2020)
SLK (Yamada et al. 2000)
WASF1 (Miki et al. 1998) – component of the WAVE1 complex
WWP2 (Bagci et al. 2020)

Literature References

PubMed ID	Title	Journal	Year
17064668	Multiple Rho proteins regulate the subcellular targeting of PAK5 Frost, JA, Wu, X	Biochem. Biophys. Res. Commun.	2006
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
12907671	The mechanism of p21-activated kinase 2 autoactivation Wu, H, Wang, ZX	J. Biol. Chem.	2003
12860998	Identification of an autoinhibitory domain of p21-activated protein kinase 5 Ching, YP, Leong, VY, Kung, HF, Wong, CM	J. Biol. Chem.	2003
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
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
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
26598554	PAK6 targets to cell-cell adhesions through its N-terminus in a Cdc42-dependent manner to drive epithelial colony escape Sun, X, Olberding, JR, Ha, BH, Calderwood, DA, Boggon, TJ, Morse, EM	J. Cell. Sci.	2016
11948177	IQGAP1 is a component of Cdc42 signaling to the cytoskeleton Swart-Mataraza, JM, Sacks, DB, Li, Z	J. Biol. Chem.	2002
9405671	WIP, a protein associated with wiskott-aldrich syndrome protein, induces actin polymerization and redistribution in lymphoid cells Geha, RS, Anton, IM, Hartwig, JH, Ramesh, N	Proc Natl Acad Sci U S A	1997
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
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
9829970	Dimerization via tandem leucine zippers is essential for the activation of the mitogen-activated protein kinase kinase kinase, MLK-3 Lassam, N, Leung, IW	J Biol Chem	1998
8670801	IQGAP1, a calmodulin-binding protein with a rasGAP-related domain, is a potential effector for cdc42Hs Callow, MG, Souza, B, Hart, MJ, Polakis, P	EMBO J.	1996
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
10490598	The Borgs, a new family of Cdc42 and TC10 GTPase-interacting proteins Joberty, G, Macara, IG, Perlungher, RR	Mol. Cell. Biol.	1999
15260990	Toca-1 mediates Cdc42-dependent actin nucleation by activating the N-WASP-WIP complex Gygi, SP, Kirschner, MW, Li, J, Le, Ma, Lebensohn, AM, Rohatgi, R, Ho, HY	Cell	2004
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
28860633	A CDC42-centered signaling unit is a dominant positive regulator of endothelial integrity van Nieuw Amerongen, GP, van Beusechem, VW, Amado-Azevedo, J, Hordijk, PL, van Bezu, J, van Hinsbergh, VWM, Reinhard, NR, de Menezes, RX	Sci Rep	2017
30061681	FBP17 and CIP4 recruit SHIP2 and lamellipodin to prime the plasma membrane for fast endophilin-mediated endocytosis Di Meglio, I, Boucrot, E, Krause, M, McMahon, HT, Ferreira, APA, Quintaneiro, LM, Lucken-Ardjomande Häsler, S, Chan Wah Hak, L, Khan, S, Law, AL	Nat. Cell Biol.	2018
10724160	Autoinhibition and activation mechanisms of the Wiskott-Aldrich syndrome protein Abdul-Manan, N, Kim, AS, Rosen, MK, Kakalis, LT, Liu, GA	Nature	2000
25963737	The structure of FMNL2-Cdc42 yields insights into the mechanism of lamellipodia and filopodia formation Kühn, S, Erdmann, C, Geyer, M, Rottner, K, Schwenkmezger, L, Kage, F, Steffen, A, Block, J	Nat Commun	2015
26299518	The Formin FMNL3 Controls Early Apical Specification in Endothelial Cells by Regulating the Polarized Trafficking of Podocalyxin Richards, M, Hetheridge, C, Mellor, H	Curr. Biol.	2015
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
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
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
12464619	A new constitutively active brain PAK3 isoform displays modified specificities toward Rac and Cdc42 GTPases Morin, N, Goupille, O, Barnier, JV, Rousseau, V	J. Biol. Chem.	2003
28825699	An apical MRCK-driven morphogenetic pathway controls epithelial polarity Pichaud, F, Terry, S, Matter, K, Vlassaks, E, Balda, MS, Leung, TKC, Olson, M, Zihni, C, Carlton, J	Nat. Cell Biol.	2017
16630611	The diaphanous-related formin DAAM1 collaborates with the Rho GTPases RhoA and Cdc42, CIP4 and Src in regulating cell morphogenesis and actin dynamics Richnau, N, Johansson, AS, Aspenström, P	Exp. Cell Res.	2006
11696321	Cdc42 induces filopodia by promoting the formation of an IRSp53:Mena complex Vandekerckhove, J, Driessens, M, Gevaert, K, Krugmann, S, Hall, A, Jordens, I	Curr. Biol.	2001
24584464	Mechanism of IRSp53 inhibition and combinatorial activation by Cdc42 and downstream effectors Boczkowska, M, Scita, G, Kast, DJ, Madasu, Y, Svitkina, T, Yang, C, Disanza, A, Dominguez, R	Nat. Struct. Mol. Biol.	2014
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