RHO GTPases activate IQGAPs

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Homo sapiens
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IQGAPs constitute a family of scaffolding proteins characterized by a calponin homology (CH) domain, a polyproline binding region (WW domain), a tandem of four IQ (isoleucine and glutamine-rich) repeats and a RAS GTPase-activating protein-related domain (GRD). Three IQGAPs have been identified in human, IQGAP1, IQGAP2 and IQGAP3. The best characterized is IQGAP1 and over 90 proteins have been reported to bind to it. IQGAPs integrate multiple signaling pathways and coordinate a large variety of cellular activities (White et al. 2012). IQGAP proteins IQGAP1, IQGAP2 and IQGAP3, bind activated RHO GTPases RAC1 and CDC42 via their GRD and stabilize them in their GTP-bound state (Kuroda et al. 1996, Swart-Mataraza et al. 2002, Wang et al. 2007). IQGAPs bind F-actin filaments via the CH domain and modulate cell shape and motility through regulation of G-actin/F-actin equilibrium (Brill et al. 1996, Fukata et al. 1997, Bashour et al. 1997, Wang et al. 2007, Pelikan-Conchaudron et al. 2011). Binding of IQGAPs to F-actin is inhibited by calmodulin binding to the IQ repeats (Bashour et al. 1997, Pelikan-Conchaudron et al. 2011). Based on IQGAP1 studies, IQGAPs presumably function as homodimers (Bashour et al. 1997).

IQGAP1 is involved in the regulation of adherens junctions through its interaction with E-cadherin (CDH1) and catenins (CTTNB1 and CTTNA1) (Kuroda et al. 1998, Hage et al. 2009). IQGAP1 contributes to cell polarity and lamellipodia formation through its interaction with microtubules (Fukata et al. 2002, Suzuki and Takahashi 2008).

Literature References
PubMed ID Title Journal Year
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
11948177 IQGAP1 is a component of Cdc42 signaling to the cytoskeleton

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

J. Biol. Chem. 2002
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
22182509 IQGAP1 and its binding proteins control diverse biological functions

White, CD, Erdemir, HH, Sacks, DB

Cell. Signal. 2012
9199170 IQGAP1, a Rac- and Cdc42-binding protein, directly binds and cross-links microfilaments

Bloom, GS, Fullerton, AT, Hart, MJ, Bashour, AM

J. Cell Biol. 1997
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
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
9368021 Regulation of cross-linking of actin filament by IQGAP1, a target for Cdc42

Kikuchi, A, Kaibuchi, K, Fukata, M, Kuroda, S, Nakamura, T, Shoji, I, Fujii, K, Matsuura, Y, Okawa, K, Iwamatsu, A

J. Biol. Chem. 1997
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