Table 2.
Cell surface receptors whose signaling is modulated by IQGAP, and implications in physiology and pathology
| Receptor | Interaction in cellsa | Direct bindingb | Binding site on IQGAP1 | Signaling outcome | Physiological and/or pathological implications | Referencec |
|---|---|---|---|---|---|---|
| IQGAP1 | ||||||
| Receptor tyrosine kinases | ||||||
| Axl | Yes | Yes | IQ | Inhibits Axl activation and signaling to Akt | n.d. | Gorisse et al., 2018 |
| EGFR | Yes | Yes | IQ | Promotes EGFR activation and signaling to ERK, Akt, STAT, and GTPases | Drives tumorigenesis | McNulty et al., 2011 |
| FGFR1 | Yes | Yes | n.d. | Stimulates N-WASP and B-Raf; promotes cell motility | n.d. | Benseñor et al., 2007 |
| HER2 | Yes | Yes | IQ | Sustains active HER2; induces resistance to trastuzumab | Promotes breast tumorigenesis | White et al., 2011 |
| IGF-1R | n.d. | n.d. | IQd | n.d. | n.d. | Salvi et al., 2022 |
| IR | Yes | Yes | IQ | Increases IR signaling to Akt and ERK | Regulates glucose homeostasis; may contribute to diabetes | Chawla et al., 2017 |
| MET | Yes | Yes | n.d. | Inhibits MET signaling; promotes Tyr phosphorylation of IQGAP1 | Influences HGF/MET-induced tumorigenesis | Hedman et al., 2020 |
| PDGFR-β | Yes | n.d. | n.d. | Modulates focal adhesion assembly and cell motility | Coordinates vascular repair | Kohno et al., 2013 |
| VEGFR2 | Yes | Yes | n.d. | Loosens cell adhesion and increases cell migration; stimulates angiogenesis and neurogenesis | Contributes to macular degeneration and cancer development | Yamaoka-Tojo et al., 2004 |
| G protein–coupled receptors | ||||||
| CXCR2 | Yes | Yes | CHD | May inhibit chemotaxis | n.d. | Neel et al., 2011 |
| CXCR4 | Yes | n.d. | n.d. | Increases receptor trafficking, ERK activation, and cell migration | n.d. | Bamidele et al., 2015 |
| DOR1 | n.d. | n.d. | n.d. | Increases receptor trafficking and ERK activation | n.d. | Bamidele et al., 2015 |
| DP1 | Yes | n.d. | n.d. | Regulates DP1 trafficking; increases ERK activation | n.d. | Fréchette et al., 2021 |
| ET-1R | n.d. | n.d. | n.d. | Modulates GTPase activation; enhances cell migration, invasion, and metastasis | May promote ovarian carcinogenesis | Chellini et al., 2019 |
| GPR161 | Yes | n.d. | n.d. | Enhances cell migration and proliferation | May contribute to breast cancer | Feigin et al., 2014 |
| KISS1R | Yes | n.d. | n.d. | Stimulates EGFR transactivation | n.d. | Cvetkovic et al., 2013 |
| LGR4 | Yes | n.d. | GRD | Increases canonical and non-canonical Wnt signaling | n.d. | Carmon et al., 2014 |
| LGR5 | Yes | n.d. | GRD and C-terminus | Reduces IQGAP1 phosphorylation; increases Rac1 and actin binding | n.d. | Carmon et al., 2017 |
| LPA1 | Yes | n.d. | n.d. | Increases cell migration and invasion | n.d. | Alemayehu et al., 2013 |
| M3-mAChR | n.d. | n.d. | n.d. | Increases active Rac1; may couple M3-mAChR to actin cytoskeleton | n.d. | Ruiz-Velasco et al., 2002 |
| MOR1 | n.d. | n.d. | n.d. | Stimulates Rac1 and ERK activation | n.d. | Civciristov et al., 2019 |
| Receptor serine/threonine kinases | ||||||
| TGFβR2 | Yes | Yes | aa 1503–1657 | Promotes TGFβR2 degradation; inhibits TGFβR2 signaling | May constrain liver and bladder tumor growth | Liu et al., 2013 |
| Glutamate-gated ion channels | ||||||
| AMPAR (GluR4) | Yes | n.d. | N-terminal | May regulate cell surface targeting of GluR4 | May participate in cognitive physiology and pathology | Nuriya et al., 2005 |
| NMDAR (NR2A, NR2B) | Yes | n.d. | n.d. | Promotes cell surface targeting of NR2A; stimulates ERK signaling | Gao et al., 2011 | |
| Adhesion receptors | ||||||
| β1-integrin | Yes | n.d. | n.d. | Couples β1-integrin to Rac1, RhoA, and Arf6 GTPases | n.d. | Nakajima et al., 2005 |
| β3-integrin | Yes | Yes | n.d. | Promotes cortical actin arrangements | Controls vascular barrier protection | Bhattacharya et al., 2012 |
| CD44 | Yes | n.d. | n.d. | Links CD44 to the cytoskeleton and ERK signaling | Increases ovarian tumor cell migration | Bourguignon et al., 2005 |
| E-cadherin | Yes | Yes | RGCT | Dissociates adherens junctions | n.d. | Kuroda et al., 1998 |
| N-cadherin | Yes | n.d. | n.d | Stimulates ERK1/2 signaling; regulates cell-cell adhesion | Participates in fear memory and spermatogenesis | Lui et al., 2005 |
| VE-cadherin | Yes | n.d. | n.d. | Destabilizes adherens junctions | n.d. | Yamaoka-Tojo et al., 2006 |
| T cell receptors | ||||||
| OX40 | Yes | n.d. | C-terminal | Restrains OX40 cosignaling | May coordinate inflammation | Okuyama et al., 2020 |
| TCR | n.d. | n.d. | n.d. | Negatively regulates TCR-mediated signaling | Gorman et al., 2012 | |
| Receptor protein tyrosine phosphatases | ||||||
| PTPμ | Yes | Yes | n.d. | Regulates GTPase-dependent functions of IQGAP1 and neurite outgrowth | n.d. | Phillips-Mason et al., 2006 |
| IQGAP2 | ||||||
| DP1 | n.d. | n.d. | n.d. | Inhibits ERK | n.d. | Fréchette et al., 2021 |
| IFN-α receptor | n.d. | n.d. | n.d. | Activates NF-κB-mediated gene expression | May have antiviral actions | Brisac et al., 2016 |
| LGR4 | Yes | n.d. | n.d. | n.d. | n.d. | Carmon et al., 2014 |
| PAR | n.d. | n.d. | n.d. | Modulates cytoskeletal dynamics | n.d. | Schmidt et al., 2003 |
| VEGFR2 | n.d. | n.d. | n.d. | Stimulates VEGF production, which activates VEGFR2 signaling to Akt | Increases angiogenesis in breast cancer | Kumar et al., 2022 |
| IQGAP3 | ||||||
| DP1 | n.d. | n.d. | n.d. | Activates ERK | n.d. | Fréchette et al., 2021 |
| EGFR | n.d. | n.d. | n.d. | Stimulates EGFR activation and signaling to ERK | n.d. | Yang et al., 2014 |
| FGFR1 | n.d. | n.d. | n.d. | Activates ERK | May coordinate embryonic development | Fang et al., 2015 |
| LGR4 | Yes | n.d. | n.d. | Enhances RSPO/LGR4 signaling to Wnt/β-catenin | n.d. | Carmon et al., 2014 |
| NGFR | n.d. | n.d. | n.d. | Triggers formation of cell extensions | n.d. | Caro-Gonzalez et al., 2012 |
Abbreviations: aa, amino acids; n.d., not determined.
a
Interaction in cells was demonstrated by co-immunoprecipitation or pull-down from cell lysates, or by colocalization or proximity ligation assay in intact cells.
b
Direct binding was demonstrated using pure proteins.
c
Only the initial publication is cited here.
d
Interaction was suggested from in silico molecular docking analysis only.