Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi


Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101675


  IQGAP1 : IQ motif-containing GTPase-activating protein 1; HUMORFA01; SAR1; p195

  IQGAP2 : IQ motif-containing GTPase-activating protein 2

  IQGAP3 : IQ motif-containing GTPase-activating protein 3

Iqg1/Cyk1 in S. cerevisiae and Rng2 in S. pombe

Historical Background

In 1994, IQGAP1 was identified from a liver cDNA library, and it was named based both on the presence of IQ motifs and a region with sequence similarity to the catalytic domain of Ras GTPase-activating proteins (GAPs) (Weissbach et al. 1994). Early studies revealed that IQGAP1 did not promote GTPase activity but instead stabilizes the GTP bound forms of Cdc42 and Rac1 (Hart et al. 1996). Subsequent investigation has identified an extensive array of proteins, including components of the cytoskeleton, cell surface receptors, and signaling components, that interact with IQGAP1 (Hedman et al. 2015).


The IQGAP family of proteins is found in eukaryotes, including fungi, protists, and vertebrates (Hedman et al. 2015). Mammals express three similar proteins, termed IQGAP1, IQGAP2, and IQGAP3 (Fig. 1a). IQGAP1 is the best characterized and functions as a multidomain scaffold in numerous signaling pathways. These functions include regulation of small GTPases (Hart et al. 1996), modulation of the cytoskeleton (Fukata et al. 1997), and participation in signaling pathways such as calcium-calmodulin (Joyal et al. 1997; Li et al. 1999), mitogen-activated protein kinase (MAPK) (Roy et al. 2004, 2005; Ren et al. 2007), and phosphatidylinositol 3 kinase (PI3K)/Akt signaling (Sbroggio et al. 2011; Choi et al. 2016). The functions of IQGAP2 and IQGAP3 are less well characterized. Some studies that IQGAP2 and IQGAP3 have redundant functions with IQGAP1, such as regulation of small GTPases, while others demonstrate unique or opposing roles (discussed in Smith et al. (2015)).
IQGAP, Fig. 1

(a) Domain structure of Homo sapiens IQGAP1, IQGAP2, and IQGAP3. These proteins all contain five domains: (i) CHD, (ii) WW domain, (iii) IQ domain, (iv) GRD, and (v) RGCT. (b) Selected binding partners for distinct domains of IQGAP1 are shown


IQGAP1, IQGAP2, and IQGAP3 each contains five defined domains that form protein-protein interactions (Fig. 1a). These are (i) a calponin homology domain (CHD), (ii) a tryptophan-containing WW domain, (iii) an IQ domain containing four IQ motifs, and (iv) a GAP-related domain (GRD) that has sequence similarity to Ras GTPase-activating proteins (GAPs), and (v) a RasGAP_C-terminal domain (RGCT), which is unique to the IQGAPs (Fig. 1) (Smith et al. 2015). The GRD lacks GAP activity, as it is missing a key arginine residue (LeCour et al. 2016). Instead, the GRD associates with several GTPases and maintains them in the active GTP-bound form (Hart et al. 1996). Examples of proteins that bind to specific domains of IQGAP1 are shown in Fig. 1b.

IQGAP1 and Signaling

Interactions of distinct proteins with IQGAP1 domains allows for the scaffolding of multiple proteins into complexes, linking their activities. These enable IQGAP1 to integrate components of a single signaling pathway (e.g., MAPK or PI3K (Roy et al. 2005; Ren et al. 2007; Choi et al. 2016)) or facilitate communication between signaling molecules from different pathways.


IQGAP1 associates with several types of transmembrane receptors, including receptor tyrosine kinases (RTKs) (Yamaoka-Tojo et al. 2004; McNulty et al. 2011; Chawla et al. 2017), G-protein coupled receptors (Alemayehu et al. 2013), and integrins (Bhattacharya et al. 2012). These interactions allow IQGAP1 to regulate receptor activation (Yamaoka-Tojo et al. 2004; McNulty et al. 2011; Kohno et al. 2013) or couple receptors to intracellular components, including small GTPases (Jacquemet et al. 2013), cytoskeletal components (Bensenor et al. 2007), and signaling via Ca2+-calmodulin (McNulty et al. 2011). Association of IQGAP1 with receptors is shown in Fig. 2.
IQGAP, Fig. 2

Cellular functions of IQGAP1: IQGAP1 participates in diverse functions in mammalian cells. (i) Cytoskeletal regulation: IQGAP1 directly binds actin and associates with microtubule-binding proteins. IQGAP1 forms complexes with molecules that bind and regulate the cytoskeleton to modulate processes such as cell-cell and cell-matrix adhesion. (ii) Signaling complexes: IQGAP1 associates with multiple signaling components and promotes the assembly of complexes that facilitate communication between proteins. Examples are association with RTK, GPCR, and components of the MAPK and PI3K/Akt signaling pathways. (iii) Calcium signaling: Changes in intracellular Ca2+ concentration activates selected Ca2+-binding proteins. Association of these Ca2+-binding proteins can regulate the interactions of IQGAP1 with other signaling molecules. (iv) Transcription: IQGAP1 directly interacts with several transcription regulatory proteins. These interactions with IQGAP1 can promote (ERα, Nrf2, β-cat) or inhibit (Yap) their functions in transcription

Small GTPases

Small GTPases function as molecular switches that are activated by GTP binding and inactivated by hydrolysis of GTP to GDP (Jaffe and Hall 2005). Several studies have identified IQGAP1 as a binding partner for the Rho family GTPases Rac1 and Cdc42 (Hart et al. 1996). GTPases, such as Rac1 and Cdc42, regulate multiple processes, including cytokinesis, cell migration, adhesion, and polarity (Jaffe and Hall 2005). IQGAP1 links GTPases to the cytoskeleton (Swart-Mataraza et al. 2002) in processes like cell migration (Mataraza et al. 2003) and cell-cell adhesion (Kuroda et al. 1999).

In addition, the RGCT of IQGAP1 associates with several GAPs and guanine nucleotide exchange factors (GEFs), which regulate small GTPase activity (Jaffe and Hall 2005). These interactions provide an additional mechanism by which IQGAP1 can modulate GTPases in processes such as cell migration (Jacquemet et al. 2013) and smooth muscle contraction (Bhattacharya et al. 2014). Roles for IQGAP1 with small GTPases are depicted in Fig. 2.


IQGAP1 directly associates via its CHD domain with F-actin (Fukata et al. 1997). IQGAP1 also interacts with several actin regulatory proteins, including Arp2/3 (Bensenor et al. 2007), N-WASP (Bensenor et al. 2007), and mDia1 (Brandt et al. 2007), which promote actin branching and polymerization. Furthermore, the IQGAP1 RGCT associates with microtubule-binding proteins, such as CLIP-170, CLASP2, and APC (reviewed in Briggs and Sacks (2003), Hedman et al. (2015)). Thus, IQGAP1 can connect F-actin to microtubule components of the cytoskeleton.

Cytoskeletal regulation by IQGAP1 is evident in several cellular processes. During cell migration, IQGAP1 localizes to the forward-moving leading edge of the cell plasma membrane (Mataraza et al. 2003). There, IQGAP1 associates with proteins that stimulate actin organization needed for migration (reviewed in Smith et al. (2015)). IQGAP1 also interacts with cell adhesion molecules known as integrins that link the extracellular matrix to the intracellular cytoskeleton. IQGAP1 forms a complex with β1 integrin and Rac1 that regulates actin stability in this complex (Suzuki et al. 2005). At cell-cell adhesions, IQGAP1 interacts with E-cadherin and β-catenin molecules, to modulate their association with the actin cytoskeleton (Kuroda et al. 1998). IQGAP1 cytoskeletal regulation is shown in Fig. 2(i).


Calmodulin binds predominantly to the IQ region of IQGAP1, and this interaction is regulated by Ca2+. In the presence of Ca2+-calmodulin, the association of IQGAP1 with many binding proteins is inhibited. For example, Ca2+-calmodulin reduces the interaction of IQGAP1 with Cdc42 (Joyal et al. 1997), Rap1 (Jeong et al. 2007), and B-Raf (Ren et al. 2008). Other Ca2+ binding proteins, e.g., S100P (Heil et al. 2010), also bind IQGAP1 and regulate its function. The role of Ca2+ in IQGAP1 function is shown in Fig. 2(iii).


The MAPK pathway regulates cell proliferation and survival. A phosphorylation cascade involving sequential kinases ultimately leads to phosphorylation and activation of the ERK1/2 kinases that modulate cytoplasmic and nuclear proteins. IQGAP1 binds several molecules in the MAPK pathway, including RTKs, K-Ras (Matsunaga et al. 2014), B-Raf (Ren et al. 2008), MEK (Roy et al. 2005), and ERK (Roy et al. 2004, 2005). Evidence reveals that IQGAP1 is a scaffold in the MAPK pathway (Roy et al. 2005) and is required for EGF to activate B-Raf (Ren et al. 2007). Interacting partners can affect IQGAP1 in MAPK signaling. For example, Ca2+-calmodulin attenuates B-Raf binding to IQGAP1, thereby reducing MAPK signaling (Ren et al. 2008).


Growth factors and other stimuli promote the activation of PI3K, which synthesizes the lipid signal phosphatidylinositol trisphosphate to activate signaling molecules like Akt kinase, a critical regulator of cell survival. Several reports show that IQGAP1 interacts with Akt and loss of IQGAP1 reduces Akt activation in response to stimuli (Sbroggio et al. 2011; Choi et al. 2016). Furthermore, IQGAP1 was recently shown to scaffold components of the PI3K cascade, thereby influencing PI3K activation (Choi et al. 2016). The role of IQGAP1 in facilitating the formation of signaling complexes is shown in Fig. 2(ii).


IQGAP1 associates with a number of transcriptional regulatory proteins, including estrogen receptor-α (ER-α) (Erdemir et al. 2014), β-catenin (Kuroda et al. 1998; Briggs et al. 2002), and Nrf2 (Kim et al. 2013) and promotes their transcriptional activity. Conversely, loss of IQGAP1 enhances nuclear factor of activated T-cells (NFAT) (Sharma et al. 2011) activity. Similarly, recent work has demonstrated that IQGAP1 binds to YAP, a component of the Hippo pathway, and loss of IQGAP1 promotes YAP transcriptional activity (Sayedyahossein et al. 2016). The role of IQGAP1 in transcription is shown in Fig. 2(iv).

Role in Physiology

In vitro studies implicate IQGAP1 in numerous processes, but initial reports detected only gastric hyperplasia in IQGAP1 knockout mice (Li et al. 2000). However, subsequent studies of these animals have identified disruption of several signaling processes modulated by IQGAP1. For example, increased aortic pressure leads to cardiac remodeling and hypertrophy, which is mediated by MAPK and Akt signaling. Loss of IQGAP1 reduces activation of these pathways leading to unfavorable cardiac remodeling (Sbroggio et al. 2011). Insulin activates MAPK and Akt, and IQGAP1-null cells display impaired insulin-stimulated activation of these pathways. Akt is a critical regulator of glucose uptake, and insulin-treated IQGAP1-null mice have reduced Akt activation in tissues and impaired glucose homeostasis (Chawla et al. 2017). These results demonstrate that IQGAP1 regulates the same signaling pathways in multiple tissues, yet the stimuli and functional outcomes may differ. In blood vessels, IQGAP1 associates with VEGFR2, β3 integrin, small GTPases, and the cytoskeleton to maintain functional vascular barriers. These structures are impaired in IQGAP1-null mice (Yamaoka-Tojo et al. 2004). In smooth muscle tissue, IQGAP1 regulates RhoA activity by recruitment of RhoGAP-p190A that regulates muscle contraction (Bhattacharya et al. 2014). Loss of IQGAP1 enhances RhoA function and smooth muscle contractility leading to excessive airway muscle contraction. These examples illustrate some IQGAP1 functions in tissues, where it can form signaling complexes that regulate tissue homeostasis in response to diverse stimuli.

IQGAP1 in Cancer

IQGAP1 is overexpressed in several cancers and appears to function as an oncogene (reviewed in White et al. (2009)). In malignant cells, IQGAP1 promotes MAPK (Jadeski et al. 2008), Akt (Chen et al. 2010), and PI3K (Choi et al. 2016) signaling that may favor tumor growth, proliferation, survival, and invasion. In addition, IQGAP1 may promote metastasis by destabilizing cell-cell contacts and enhancing activity of small GTPases (Mataraza et al. 2003; Jadeski et al. 2008).

IQGAP1 in Microbial Pathogenesis

An accumulating body of evidence implicates IQGAP1 in microbial pathogenesis. Certain microbes manipulate selected host cell signaling pathways to facilitate infection. IQGAP1 associates with several molecules that contribute to microbial pathogenesis. This concept was initially described for Salmonella typhimurium, which usurps IQGAP1 both to enter host cells (Brown et al. 2007) and to impair immune response, thereby establishing chronic infection (McLaughlin et al. 2009). Subsequent evidence revealed that other bacteria and viruses target IQGAP1 for pathogenesis. Bacteria manipulate IQGAP1 to alter several cellular pathways, including actin, Cdc42, Rac1, and MAPK (reviewed in Kim et al. 2011) function during infection.


IQGAP1 serves as a signaling platform through the formation of multiple protein-protein interactions. By associating with >130 proteins, IQGAP1 integrates diverse signaling pathways and is integral to numerous fundamental cellular processes, ranging from angiogenesis and renal glomerular filtration to neurite outgrowth and insulin secretion. Disruption of normal IQGAP1 homeostasis and function may contribute to pathology, e.g., cancer, diabetes, cardiac disease, and infections. Collectively, these observations suggest that IQGAP1 may be a target for the development of new therapeutic modalities for these conditions.



Work in the authors’ laboratory is funded by the Intramural Research Program of the National Institutes of Health.


  1. Alemayehu M, Dragan M, Pape C, Siddiqui I, Sacks DB, Di Guglielmo GM, et al. β-arrestin2 regulates lysophosphatidic acid-induced human breast tumor cell migration and invasion via Rap1 and IQGAP1. PLoS One. 2013;8:e56174. doi: 10.1371/journal.pone.0056174. [pii] PONE-D-12-23671.PubMedCrossRefPubMedCentralGoogle Scholar
  2. Bensenor LB, Kan HM, Wang N, Wallrabe H, Davidson LA, Cai Y, et al. IQGAP1 regulates cell motility by linking growth factor signaling to actin assembly. J Cell Sci. 2007;120:658–69. doi: 10.1242/jcs.03376. [pii] jcs.03376.PubMedCrossRefGoogle Scholar
  3. Bhattacharya M, Su G, Su X, Oses-Prieto JA, Li JT, Huang X, et al. IQGAP1 is necessary for pulmonary vascular barrier protection in murine acute lung injury and pneumonia. Am J Physiol Lung Cell Mol Physiol. 2012;303:L12–9. doi: 10.1152/ajplung.00375.2011. [pii] ajplung.00375.2011.PubMedCrossRefPubMedCentralGoogle Scholar
  4. Bhattacharya M, Sundaram A, Kudo M, Farmer J, Ganesan P, Khalifeh-Soltani A, et al. IQGAP1-dependent scaffold suppresses RhoA and inhibits airway smooth muscle contraction. J Clin Invest. 2014;124:4895–8. doi: 10.1172/JCI76658.PubMedCrossRefPubMedCentralGoogle Scholar
  5. Brandt DT, Marion S, Griffiths G, Watanabe T, Kaibuchi K, Grosse R. Dia1 and IQGAP1 interact in cell migration and phagocytic cup formation. J Cell Biol. 2007;178:193–200. doi: 10.1083/jcb.200612071. [pii] jcb.200612071.PubMedCrossRefPubMedCentralGoogle Scholar
  6. Briggs MW, Sacks DB. IQGAP proteins are integral components of cytoskeletal regulation. EMBO Rep. 2003;4:571–4. doi: 10.1038/sj.embor.embor867. [pii] embor867.PubMedCrossRefPubMedCentralGoogle Scholar
  7. Briggs MW, Li Z, Sacks DB. IQGAP1-mediated stimulation of transcriptional co-activation by beta-catenin is modulated by calmodulin. J Biol Chem. 2002;277:7453–65. doi: 10.1074/jbc.M104315200. [pii] M104315200.PubMedCrossRefGoogle Scholar
  8. Brown MD, Bry L, Li Z, Sacks DB. IQGAP1 regulates Salmonella invasion through interactions with actin, Rac1, and Cdc42. J Biol Chem. 2007;282:30265–72. doi: 10.1074/jbc.M702537200. [pii] M702537200.PubMedCrossRefGoogle Scholar
  9. Chawla B, Hedman AC, Sayedyahossein S, Erdemir HH, Li Z, Sacks DB. Absence of IQGAP1 leads to insulin resistance. J Biol Chem. 2017;292:3273–89. doi: 10.1074/jbc.M116.752642.PubMedCrossRefPubMedCentralGoogle Scholar
  10. Chen F, Zhu HH, Zhou LF, Wu SS, Wang J, Chen Z. IQGAP1 is overexpressed in hepatocellular carcinoma and promotes cell proliferation by Akt activation. Exp Mol Med. 2010;42:477–83. doi: 10.3858/emm.2010.42.7.049. [pii] 2010.42.049.PubMedCrossRefPubMedCentralGoogle Scholar
  11. Choi S, Hedman AC, Sayedyahossein S, Thapa N, Sacks DB, Anderson RA. Agonist-stimulated phosphatidylinositol-3,4,5-trisphosphate generation by scaffolded phosphoinositide kinases. Nat Cell Biol. 2016;18:1324–35. doi: 10.1038/ncb3441.PubMedCrossRefPubMedCentralGoogle Scholar
  12. Erdemir HH, Li Z, Sacks DB. IQGAP1 binds to estrogen receptor-alpha and modulates its function. J Biol Chem. 2014;289:9100–12. doi: 10.1074/jbc.M114.553511. [pii] M114.553511.PubMedCrossRefPubMedCentralGoogle Scholar
  13. Fukata M, Kuroda S, Fujii K, Nakamura T, Shoji I, Matsuura Y, et al. Regulation of cross-linking of actin filament by IQGAP1, a target for Cdc42. J Biol Chem. 1997;272:29579–83.PubMedCrossRefGoogle Scholar
  14. Hart MJ, Callow MG, Souza B, Polakis P. IQGAP1, a calmodulin-binding protein with a rasGAP-related domain, is a potential effector for cdc42Hs. EMBO J. 1996;15:2997–3005.PubMedPubMedCentralGoogle Scholar
  15. Hedman AC, Smith JM, Sacks DB. The biology of IQGAP proteins: beyond the cytoskeleton. EMBO Rep. 2015;16:427–46. doi: 10.15252/embr.201439834.PubMedCrossRefPubMedCentralGoogle Scholar
  16. Heil A, Nazmi AR, Koltzscher M, Poeter M, Austermann J, Assard N, et al. S100P is a novel interaction partner and regulator of IQGAP1. J Biol Chem. 2010;286:7227–38. doi: 10.1074/jbc.M110.135095. [pii] M110.135095.PubMedCrossRefPubMedCentralGoogle Scholar
  17. Jacquemet G, Morgan MR, Byron A, Humphries JD, Choi CK, Chen CS, et al. Rac1 is deactivated at integrin activation sites through an IQGAP1-filamin-A-RacGAP1 pathway. J Cell Sci. 2013;126:4121–35. doi: 10.1242/jcs.121988. [pii] jcs.121988.PubMedCrossRefPubMedCentralGoogle Scholar
  18. Jadeski L, Mataraza JM, Jeong HW, Li Z, Sacks DB. IQGAP1 stimulates proliferation and enhances tumorigenesis of human breast epithelial cells. J Biol Chem. 2008;283:1008–17. doi: 10.1074/jbc.M708466200. [pii] M708466200.PubMedCrossRefGoogle Scholar
  19. Jaffe AB, Hall A. Rho GTPases: biochemistry and biology. Annu Rev Cell Dev Biol. 2005;21:247–69. doi: 10.1146/annurev.cellbio.21.020604.150721.PubMedCrossRefGoogle Scholar
  20. Jeong HW, Li Z, Brown MD, Sacks DB. IQGAP1 binds Rap1 and modulates its activity. J Biol Chem. 2007;282:20752–62. doi: 10.1074/jbc.M700487200. [pii] M700487200.PubMedCrossRefGoogle Scholar
  21. Joyal JL, Annan RS, Ho YD, Huddleston ME, Carr SA, Hart MJ, et al. Calmodulin modulates the interaction between IQGAP1 and Cdc42. Identification of IQGAP1 by nanoelectrospray tandem mass spectrometry. J Biol Chem. 1997;272:15419–25.PubMedCrossRefGoogle Scholar
  22. Kim H, White CD, Li Z, Sacks DB. Salmonella enterica serotype Typhimurium usurps the scaffold protein IQGAP1 to manipulate Rac1 and MAPK signalling. Biochem J. 2011;440:309–18. doi: 10.1042/BJ20110419. [pii] BJ20110419.PubMedCrossRefPubMedCentralGoogle Scholar
  23. Kim JH, Xu EY, Sacks DB, Lee J, Shu L, Xia B, et al. Identification and functional studies of a new Nrf2 partner IQGAP1: a critical role in the stability and transactivation of Nrf2. Antioxid Redox Signal. 2013;19:89–101. doi: 10.1089/ars.2012.4586.PubMedCrossRefPubMedCentralGoogle Scholar
  24. Kohno T, Urao N, Ashino T, Sudhahar V, Inomata H, Yamaoka-Tojo M, et al. IQGAP1 links PDGF receptor-beta signal to focal adhesions involved in vascular smooth muscle cell migration: role in neointimal formation after vascular injury. Am J Physiol Cell Physiol. 2013;305:C591–600. doi: 10.1152/ajpcell.00011.2013. [pii] ajpcell.00011.2013.PubMedCrossRefPubMedCentralGoogle Scholar
  25. Kuroda S, Fukata M, Nakagawa M, Fujii K, Nakamura T, Ookubo T, et al. Role of IQGAP1, a target of the small GTPases Cdc42 and Rac1, in regulation of E-cadherin- mediated cell-cell adhesion. Science. 1998;281:832–5.PubMedCrossRefGoogle Scholar
  26. Kuroda S, Fukata M, Nakagawa M, Kaibuchi K. Cdc42, Rac1, and their effector IQGAP1 as molecular switches for cadherin-mediated cell-cell adhesion. Biochem Biophys Res Commun. 1999;262:1–6. doi: 10.1006/bbrc.1999.1122. [pii] S0006-291X(99)91122-1.PubMedCrossRefGoogle Scholar
  27. LeCour Jr L, Boyapati VK, Liu J, Li Z, Sacks DB, Worthylake DK. The structural basis for Cdc42-induced dimerization of IQGAPs. Structure. 2016;24:1499–508. doi: 10.1016/j.str.2016.06.016.PubMedCrossRefPubMedCentralGoogle Scholar
  28. Li Z, Kim SH, Higgins JM, Brenner MB, Sacks DB. IQGAP1 and calmodulin modulate E-cadherin function. J Biol Chem. 1999;274:37885–92.PubMedCrossRefGoogle Scholar
  29. Li S, Wang Q, Chakladar A, Bronson RT, Bernards A. Gastric hyperplasia in mice lacking the putative Cdc42 effector IQGAP1. Mol Cell Biol. 2000;20:697–701.PubMedCrossRefPubMedCentralGoogle Scholar
  30. Mataraza JM, Briggs MW, Li Z, Entwistle A, Ridley AJ, Sacks DB. IQGAP1 promotes cell motility and invasion. J Biol Chem. 2003;278:41237–45. doi: 10.1074/jbc.M304838200. [pii] M304838200.PubMedCrossRefGoogle Scholar
  31. Matsunaga H, Kubota K, Inoue T, Isono F, Ando O. IQGAP1 selectively interacts with K-Ras but not with H-Ras and modulates K-Ras function. Biochem Biophys Res Commun. 2014;444:360–4. doi: 10.1016/j.bbrc.2014.01.041. [pii] S0006-291X(14)00065-5.PubMedCrossRefGoogle Scholar
  32. McLaughlin LM, Govoni GR, Gerke C, Gopinath S, Peng K, Laidlaw G, et al. The Salmonella SPI2 effector SseI mediates long-term systemic infection by modulating host cell migration. PLoS Pathog. 2009;5:e1000671. doi: 10.1371/journal.ppat.1000671.PubMedCrossRefPubMedCentralGoogle Scholar
  33. McNulty DE, Li Z, White CD, Sacks DB, Annan RS. MAPK scaffold IQGAP1 binds the EGF receptor and modulates its activation. J Biol Chem. 2011;286:15010–21. doi: 10.1074/jbc.M111.227694. [pii] M111.227694.PubMedCrossRefPubMedCentralGoogle Scholar
  34. Ren JG, Li Z, Sacks DB. IQGAP1 modulates activation of B-Raf. Proc Natl Acad Sci USA. 2007;104:10465–9. doi: 10.1073/pnas.0611308104. [pii] 0611308104.PubMedCrossRefPubMedCentralGoogle Scholar
  35. Ren JG, Li Z, Sacks DB. IQGAP1 integrates Ca2+/calmodulin and B-Raf signaling. J Biol Chem. 2008;283:22972–82. doi: 10.1074/jbc.M804626200. [pii] M804626200.PubMedCrossRefPubMedCentralGoogle Scholar
  36. Roy M, Li Z, Sacks DB. IQGAP1 binds ERK2 and modulates its activity. J Biol Chem. 2004;279:17329–37. doi: 10.1074/jbc.M308405200. [pii] M308405200.PubMedCrossRefGoogle Scholar
  37. Roy M, Li Z, Sacks DB. IQGAP1 is a scaffold for mitogen-activated protein kinase signaling. Mol Cell Biol. 2005;25:7940–52. doi: 10.1128/MCB.25.18.7940-7952.2005. [pii] 25/18/7940.PubMedCrossRefPubMedCentralGoogle Scholar
  38. Sayedyahossein S, Li Z, Hedman AC, Morgan CJ, Sacks DB. IQGAP1 binds to yes-associated protein (YAP) and modulates its transcriptional activity. J Biol Chem. 2016;291:19261–73. doi: 10.1074/jbc.M116.732529.PubMedCrossRefPubMedCentralGoogle Scholar
  39. Sbroggio M, Carnevale D, Bertero A, Cifelli G, De Blasio E, Mascio G, et al. IQGAP1 regulates ERK1/2 and AKT signalling in the heart and sustains functional remodelling upon pressure overload. Cardiovasc Res. 2011;91:456–64. doi: 10.1093/cvr/cvr103. [pii] cvr103.PubMedCrossRefPubMedCentralGoogle Scholar
  40. Sharma S, Findlay GM, Bandukwala HS, Oberdoerffer S, Baust B, Li Z, et al. Dephosphorylation of the nuclear factor of activated T cells (NFAT) transcription factor is regulated by an RNA-protein scaffold complex. Proc Natl Acad Sci USA. 2011;108:11381–6. doi: 10.1073/pnas.1019711108. [pii] 1019711108.PubMedCrossRefPubMedCentralGoogle Scholar
  41. Smith JM, Hedman AC, Sacks DB. IQGAPs choreograph cellular signaling from the membrane to the nucleus. Trends Cell Biol. 2015;25:171–84. doi: 10.1016/j.tcb.2014.12.005.PubMedCrossRefPubMedCentralGoogle Scholar
  42. Suzuki K, Chikamatsu Y, Takahashi K. Requirement of protein phosphatase 2A for recruitment of IQGAP1 to Rac-bound beta1 integrin. J Cell Physiol. 2005;203:487–92. doi: 10.1002/jcp.20249.PubMedCrossRefGoogle Scholar
  43. Swart-Mataraza JM, Li Z, Sacks DB. IQGAP1 is a component of Cdc42 signaling to the cytoskeleton. J Biol Chem. 2002;277:24753–63. doi: 10.1074/jbc.M111165200. [pii] M111165200.PubMedCrossRefGoogle Scholar
  44. Weissbach L, Settleman J, Kalady MF, Snijders AJ, Murthy AE, Yan YX, et al. Identification of a human rasGAP-related protein containing calmodulin-binding motifs. J Biol Chem. 1994;269:20517–21.PubMedGoogle Scholar
  45. White CD, Brown MD, Sacks DB. IQGAPs in cancer: a family of scaffold proteins underlying tumorigenesis. FEBS Lett. 2009;583:1817–24. doi: 10.1016/j.febslet.2009.05.007. [pii] S0014-5793(09)00373-1.PubMedCrossRefPubMedCentralGoogle Scholar
  46. Yamaoka-Tojo M, Ushio-Fukai M, Hilenski L, Dikalov SI, Chen YE, Tojo T, et al. IQGAP1, a novel vascular endothelial growth factor receptor binding protein, is involved in reactive oxygen species-dependent endothelial migration and proliferation. Circ Res. 2004;95:276–83. doi: 10.1161/01.RES.0000136522.58649.60. [pii] 01.RES.0000136522.58649.60.PubMedCrossRefGoogle Scholar

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© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of Laboratory MedicineNational Institutes of HealthBethesdaUSA