Integrin alpha-5

Definition:

Integrin alpha-5/beta-1 (ITGA5:ITGB1) is a receptor for fibronectin and fibrinogen. It recognizes the sequence R-G-D in its ligands. ITGA5:ITGB1 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. ITGA5:ITGB1 acts as a receptor for fibrillin-1 (FBN1) and mediates R-G-D-dependent cell adhesion to FBN1. ITGA5:ITGB1 is a receptor for IL1B and binding is essential for IL1B signaling. ITGA5:ITGB3 is a receptor for soluble CD40LG and is required for CD40/CD40LG signaling.; (Microbial infection) Integrin ITGA5:ITGB1 acts as a receptor for Human metapneumovirus.; (Microbial infection) Integrin ITGA2:ITGB1 acts as a receptor for Human parvovirus B19.; (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]. 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]

[4]. 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]

[5]. 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]

[6]. Yongwei Wei, et al. Roles of the putative integrin-binding motif of the human metapneumovirus fusion (f) protein in cell-cell fusion, viral infectivity, and pathogenesis. J Virol. 2014 Apr;88(8):4338-52. [Content Brief]

[7]. Kirsten A Weigel-Kelley, et al. Alpha5beta1 integrin as a cellular coreceptor for human parvovirus B19: requirement of functional activation of beta1 integrin for viral entry. Blood. 2003 Dec 1;102(12):3927-33. [Content Brief]

[8]. 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]

[9]. 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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