Integrin alpha-V

Definition:

The alpha-V (ITGAV) integrins are receptors for vitronectin, cytotactin, fibronectin, fibrinogen, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin and vWF. They recognize the sequence R-G-D in a wide array of ligands. ITGAV:ITGB3 binds to fractalkine (CX3CL1) and may act as its coreceptor in CX3CR1-dependent fractalkine signaling. ITGAV:ITGB3 binds to NRG1 (via EGF domain) and this binding is essential for NRG1-ERBB signaling. ITGAV:ITGB3 binds to FGF1 and this binding is essential for FGF1 signaling. ITGAV:ITGB3 binds to FGF2 and this binding is essential for FGF2 signaling. ITGAV:ITGB3 binds to IGF1 and this binding is essential for IGF1 signaling. ITGAV:ITGB3 binds to IGF2 and this binding is essential for IGF2 signaling. ITGAV:ITGB3 binds to IL1B and this binding is essential for IL1B signaling. ITGAV:ITGB3 binds to PLA2G2A via a site (site 2) which is distinct from the classical ligand-binding site (site 1) and this induces integrin conformational changes and enhanced ligand binding to site 1. ITGAV:ITGB3 and ITGAV:ITGB6 act as receptors for fibrillin-1 (FBN1) and mediate R-G-D-dependent cell adhesion to FBN1. Integrin alpha-V/beta-6 or alpha-V/beta-8 (ITGAV:ITGB6 or ITGAV:ITGB8) mediates R-G-D-dependent release of transforming growth factor beta-1 (TGF-beta-1) from regulatory Latency-associated peptide (LAP), thereby playing a key role in TGF-beta-1 activation. ITGAV:ITGB3 acts as a receptor for CD40LG.; (Microbial infection) Integrin ITGAV:ITGB5 acts as a receptor for Adenovirus type C.; (Microbial infection) Integrin ITGAV:ITGB5 and ITGAV:ITGB3 act as receptors for Coxsackievirus A9 and B1.; (Microbial infection) Integrin ITGAV:ITGB3 acts as a receptor for Herpes virus 8/HHV-8.; (Microbial infection) Integrin ITGAV:ITGB6 acts as a receptor for herpes simplex 1/HHV-1.; (Microbial infection) Integrin ITGAV:ITGB3 acts as a receptor for Human parechovirus 1.; (Microbial infection) Integrin ITGAV:ITGB3 acts as a receptor for West nile virus.; (Microbial infection) In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions.

References:

[1]. Masaaki Fujita, et al. Proinflammatory secreted phospholipase A2 type IIA (sPLA-IIA) induces integrin activation through direct binding to a newly identified binding site (site 2) in integrins αvβ3, α4β1, and α5β1. J Biol Chem. 2015 Jan 2;290(1):259-71. [Content Brief]

[2]. G Barillari, et al. The Tat protein of human immunodeficiency virus type-1 promotes vascular cell growth and locomotion by engaging the alpha5beta1 and alphavbeta3 integrins and by mobilizing sequestered basic fibroblast growth factor. Blood. 1999 Jul 15;94(2):663-72. [Content Brief]

[3]. P Joki-Korpela, et al. Entry of human parechovirus 1. J Virol. 2001 Feb;75(4):1958-67. [Content Brief]

[4]. Rui Wang, et al. GARP regulates the bioavailability and activation of TGFβ. Mol Biol Cell. 2012 Mar;23(6):1129-39. [Content Brief]

[5]. Xianchi Dong, et al. Force interacts with macromolecular structure in activation of TGF-β. Nature. 2017 Feb 2;542(7639):55-59. [Content Brief]

[6]. Cynthia Lyle, et al. Integrin alphavbeta5 is a primary receptor for adenovirus in CAR-negative cells. Virol J. 2010 Jul 8;7:148. [Content Brief]

[7]. Ciğdem H Williams, et al. Integrin alpha v beta 6 is an RGD-dependent receptor for coxsackievirus A9. J Virol. 2004 Jul;78(13):6967-73. [Content Brief]

[8]. Katja Schmidt, et al. Integrins modulate the infection efficiency of West Nile virus into cells. J Gen Virol. 2013 Aug;94(Pt 8):1723-1733. [Content Brief]

[9]. Seiji Mori, et al. Direct binding of integrin alphavbeta3 to FGF1 plays a role in FGF1 signaling. J Biol Chem. 2008 Jun 27;283(26):18066-75. [Content Brief]

[10]. M V Agrez, et al. Integrin alpha v beta 6 enhances coxsackievirus B1 lytic infection of human colon cancer cells. Virology. 1997 Dec 8;239(1):71-7. [Content Brief]

[11]. Seiji Mori, et al. The integrin-binding defective FGF2 mutants potently suppress FGF2 signalling and angiogenesis. Biosci Rep. 2017 Apr 10;37(2):BSR20170173. [Content Brief]

[12]. Yoko K Takada, et al. Integrin Binding to the Trimeric Interface of CD40L Plays a Critical Role in CD40/CD40L Signaling. J Immunol. 2019 Sep 1;203(5):1383-1391. [Content Brief]

[13]. Justin P Annes, et al. Integrin alphaVbeta6-mediated activation of latent TGF-beta requires the latent TGF-beta binding protein-1. J Cell Biol. 2004 Jun 7;165(5):723-34. [Content Brief]

[14]. M Roivainen, et al. Entry of coxsackievirus A9 into host cells: specific interactions with alpha v beta 3 integrin, the vitronectin receptor. Virology. 1994 Sep;203(2):357-65. [Content Brief]

[15]. Jun Saegusa, et al. The direct binding of insulin-like growth factor-1 (IGF-1) to integrin alphavbeta3 is involved in IGF-1 signaling. J Biol Chem. 2009 Sep 4;284(36):24106-14. [Content Brief]

[16]. Daniel V Bax, et al. Cell adhesion to fibrillin-1 molecules and microfibrils is mediated by alpha 5 beta 1 and alpha v beta 3 integrins. J Biol Chem. 2003 Sep 5;278(36):34605-16. [Content Brief]

[17]. Tatiana Gianni, et al. αvβ6- and αvβ8-integrins serve as interchangeable receptors for HSV gH/gL to promote endocytosis and activation of membrane fusion. PLoS Pathog. 2013;9(12):e1003806. [Content Brief]

[18]. Yoko K Takada, et al. Direct binding to integrins and loss of disulfide linkage in interleukin-1β (IL-1β) are involved in the agonistic action of IL-1β. J Biol Chem. 2017 Dec 8;292(49):20067-20075. [Content Brief]

[19]. Masaaki Fujita, et al. Integrins αvβ3 and α4β1 act as coreceptors for fractalkine, and the integrin-binding defective mutant of fractalkine is an antagonist of CX3CR1. J Immunol. 2012 Dec 15;189(12):5809-19. [Content Brief]

[20]. H Jacques Garrigues, et al. Integrin alphaVbeta3 Binds to the RGD motif of glycoprotein B of Kaposi's sarcoma-associated herpesvirus and functions as an RGD-dependent entry receptor. J Virol. 2008 Feb;82(3):1570-80. [Content Brief]

[21]. Jelena Jovanovic, et al. alphaVbeta6 is a novel receptor for human fibrillin-1. Comparative studies of molecular determinants underlying integrin-rgd affinity and specificity. J Biol Chem. 2007 Mar 2;282(9):6743-51. [Content Brief]

[22]. Katsuaki Ieguchi, et al. Direct binding of the EGF-like domain of neuregulin-1 to integrins ({alpha}v{beta}3 and {alpha}6{beta}4) is involved in neuregulin-1/ErbB signaling. J Biol Chem. 2010 Oct 8;285(41):31388-98. [Content Brief]

[23]. Dora Maria Cedano Prieto, et al. Direct integrin binding to insulin-like growth factor-2 through the C-domain is required for insulin-like growth factor receptor type 1 (IGF1R) signaling. PLoS One. 2017 Sep 5;12(9):e0184285. [Content Brief]

[24]. Jun Saegusa, et al. Pro-inflammatory secretory phospholipase A2 type IIA binds to integrins alphavbeta3 and alpha4beta1 and induces proliferation of monocytic cells in an integrin-dependent manner. J Biol Chem. 2008 Sep 19;283(38):26107-15. [Content Brief]

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