CDC42 binds effectors at the plasma membrane

Stable Identifier
Reaction [binding]
Homo sapiens
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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 (Leung et al. 1998; Schwarz et al. 2012; Bagci et al. 2020)
CDC42BPB (Zihni et al. 2017; Bagci et al. 2020)
CDC42EP1 (Joberty et al. 1999; Bagci et al. 2020)
CDC42EP2 (Joberty et al. 1999; Bagci et al. 2020)
CDC42EP3 (Joberty et al. 1999)
CDC42EP4 (Joberty et al. 1999; Bagci et al. 2020)
CDC42EP5 (Joberty et al. 1999)
FMNL1 (Kuhn et al. 2015)
FMNL2 (Block et al. 2012; Kuhn et al. 2015)
FMNL3 (Richards et al. 2015)
FNBP1 (Chan Wah Hak et al. 2018; Bagci et al. 2020)
FNBP1L (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)
NOX1 complex (Cheng et al. 2006)
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 (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
18218625 Biochemical characterization of the Rho GTPase-regulated actin assembly by diaphanous-related formins, mDia1 and Daam1, in platelets

Higashi, T, Ikeda, T, Shirakawa, R, Kondo, H, Kawato, M, Horiguchi, M, Okuda, T, Okawa, K, Fukai, S, Nureki, O, Kita, T, Horiuchi, H

J. Biol. Chem. 2008
17064668 Multiple Rho proteins regulate the subcellular targeting of PAK5

Wu, X, Frost, JA

Biochem. Biophys. Res. Commun. 2006
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, Wong, CM, Kung, HF

J. Biol. Chem. 2003
11756552 PAK5, a new brain-specific kinase, promotes neurite outgrowth in N1E-115 cells

Dan, C, Nath, N, Liberto, M, Minden, A

Mol. Cell. Biol. 2002
9843499 WAVE, a novel WASP-family protein involved in actin reorganization induced by Rac

Miki, H, Suetsugu, S, Takenawa, T

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

Leung, T, Chen, XQ, Manser, E, Lim, L

Mol. Cell. Biol. 1996
10699464 Molecular cloning and characterization of a novel human STE20-like kinase, hSLK

Yamada, E, Tsujikawa, K, Itoh, S, Kameda, Y, Kohama, Y, Yamamoto, H

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

Morse, EM, Sun, X, Olberding, JR, Ha, BH, Boggon, TJ, Calderwood, DA

J. Cell. Sci. 2016
11948177 IQGAP1 is a component of Cdc42 signaling to the cytoskeleton

Swart-Mataraza, JM, Li, Z, Sacks, DB

J. Biol. Chem. 2002
9405671 WIP, a protein associated with wiskott-aldrich syndrome protein, induces actin polymerization and redistribution in lymphoid cells

Ramesh, N, Anton, IM, Hartwig, JH, Geha, RS

Proc Natl Acad Sci U S A 1997
22608513 FMNL2 drives actin-based protrusion and migration downstream of Cdc42

Block, J, Breitsprecher, D, Kühn, S, Winterhoff, M, Kage, F, Geffers, R, Duwe, P, Rohn, JL, Baum, B, Brakebusch, C, Geyer, M, Stradal, TE, Faix, J, Rottner, K

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

Reid, T, Furuyashiki, T, Ishizaki, T, Watanabe, G, Watanabe, N, Fujisawa, K, Morii, N, Madaule, P, Narumiya, S

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

Leung, IW, Lassam, N

J Biol Chem 1998
8670801 IQGAP1, a calmodulin-binding protein with a rasGAP-related domain, is a potential effector for cdc42Hs

Hart, MJ, Callow, MG, Souza, B, Polakis, P

EMBO J. 1996
8798539 Identification of IQGAP as a putative target for the small GTPases, Cdc42 and Rac1

Kuroda, S, Fukata, M, Kobayashi, K, Nakafuku, M, Nomura, N, Iwamatsu, A, Kaibuchi, K

J. Biol. Chem. 1996
22970203 Serine-71 phosphorylation of Rac1 modulates downstream signaling

Schwarz, J, Proff, J, Hävemeier, A, Ladwein, M, Rottner, K, Barlag, B, Pich, A, Tatge, H, Just, I, Gerhard, R

PLoS ONE 2012
11773441 AR and ER interaction with a p21-activated kinase (PAK6)

Lee, SR, Ramos, SM, Ko, A, Masiello, D, Swanson, KD, Lu, ML, Balk, SP

Mol. Endocrinol. 2002
8805223 Two GTPases, Cdc42 and Rac, bind directly to a protein implicated in the immunodeficiency disorder Wiskott-Aldrich syndrome

Aspenström, P, Lindberg, U, Hall, A

Curr Biol 1996
10490598 The Borgs, a new family of Cdc42 and TC10 GTPase-interacting proteins

Joberty, G, Perlungher, RR, Macara, IG

Mol. Cell. Biol. 1999
15260990 Toca-1 mediates Cdc42-dependent actin nucleation by activating the N-WASP-WIP complex

Ho, HY, Rohatgi, R, Lebensohn, AM, Le, Ma, Li, J, Gygi, SP, Kirschner, MW

Cell 2004
31871319 Mapping the proximity interaction network of the Rho-family GTPases reveals signalling pathways and regulatory mechanisms

Bagci, H, Sriskandarajah, N, Robert, A, Boulais, J, Elkholi, IE, Tran, V, Lin, ZY, Thibault, MP, Dubé, N, Faubert, D, Hipfner, DR, Gingras, AC, Cote, JF

Nat. Cell Biol. 2020
28860633 A CDC42-centered signaling unit is a dominant positive regulator of endothelial integrity

Amado-Azevedo, J, Reinhard, NR, van Bezu, J, de Menezes, RX, van Beusechem, VW, van Nieuw Amerongen, GP, van Hinsbergh, VWM, Hordijk, PL

Sci Rep 2017
30061681 FBP17 and CIP4 recruit SHIP2 and lamellipodin to prime the plasma membrane for fast endophilin-mediated endocytosis

Chan Wah Hak, L, Khan, S, Di Meglio, I, Law, AL, Lucken-Ardjomande Häsler, S, Quintaneiro, LM, Ferreira, APA, Krause, M, McMahon, HT, Boucrot, E

Nat. Cell Biol. 2018
10724160 Autoinhibition and activation mechanisms of the Wiskott-Aldrich syndrome protein

Kim, AS, Kakalis, LT, Abdul-Manan, N, Liu, GA, Rosen, MK

Nature 2000
25963737 The structure of FMNL2-Cdc42 yields insights into the mechanism of lamellipodia and filopodia formation

Kühn, S, Erdmann, C, Kage, F, Block, J, Schwenkmezger, L, Steffen, A, Rottner, K, Geyer, M

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

Wang, S, Watanabe, T, Noritake, J, Fukata, M, Yoshimura, T, Itoh, N, Harada, T, Nakagawa, M, Matsuura, Y, Arimura, N, Kaibuchi, K

J. Cell. Sci. 2007
11804587 Pak1 kinase homodimers are autoinhibited in trans and dissociated upon activation by Cdc42 and Rac1

Parrini, MC, Lei, M, Harrison, SC, Mayer, BJ

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

Hammond, SM, Jenco, JM, Nakashima, S, Cadwallader, K, Gu, Q, Cook, S, Nozawa, Y, Prestwich, GD, Frohman, MA, Morris, AJ

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

Brill, S, Li, S, Lyman, CW, Church, DM, Wasmuth, JJ, Weissbach, L, Bernards, A, Snijders, AJ

Mol. Cell. Biol. 1996
12464619 A new constitutively active brain PAK3 isoform displays modified specificities toward Rac and Cdc42 GTPases

Rousseau, V, Goupille, O, Morin, N, Barnier, JV

J. Biol. Chem. 2003
16636067 Nox1-dependent reactive oxygen generation is regulated by Rac1

Cheng, G, Diebold, BA, Hughes, Y, Lambeth, JD

J. Biol. Chem. 2006
28825699 An apical MRCK-driven morphogenetic pathway controls epithelial polarity

Zihni, C, Vlassaks, E, Terry, S, Carlton, J, Leung, TKC, Olson, M, Pichaud, F, Balda, MS, Matter, K

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

Aspenström, P, Richnau, N, Johansson, AS

Exp. Cell Res. 2006
11696321 Cdc42 induces filopodia by promoting the formation of an IRSp53:Mena complex

Krugmann, S, Jordens, I, Gevaert, K, Driessens, M, Vandekerckhove, J, Hall, A

Curr. Biol. 2001
24584464 Mechanism of IRSp53 inhibition and combinatorial activation by Cdc42 and downstream effectors

Kast, DJ, Yang, C, Disanza, A, Boczkowska, M, Madasu, Y, Scita, G, Svitkina, T, 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
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