Table 2. Cell surface receptors whose... | Rockefeller University Press

Table 2.

Cell surface receptors whose signaling is modulated by IQGAP, and implications in physiology and pathology

Receptor	Interaction in cells^{^a}	Direct binding^{^b}	Binding site on IQGAP1	Signaling outcome	Physiological and/or pathological implications	Reference^{^c}
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.	IQ^{^d}	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	May participate in cognitive physiology and pathology	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	May coordinate inflammation	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 cells^a	Direct binding^b	Binding site on IQGAP1	Signaling outcome	Physiological and/or pathological implications	Reference^c
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.	IQ^d	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	May participate in cognitive physiology and pathology	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	May coordinate inflammation	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.

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