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 |
| 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.
Interaction in cells was demonstrated by co-immunoprecipitation or pull-down from cell lysates, or by colocalization or proximity ligation assay in intact cells.
Direct binding was demonstrated using pure proteins.
Only the initial publication is cited here.
Interaction was suggested from in silico molecular docking analysis only.