Disease relevance of ITGA1

• Unexpectedly, the beta 1-integrins VLA-1 (1/51), VLA-2 (18/123), VLA-3 (5/43), VLA-6 (15/29) and the E-selectin (2/47) were expressed on > 70% blasts on a subset of leukemias of varied phenotype [1].
• VLA1 and VLA5 were widely distributed in benign and malignant mesenchymal tumors and in the desmoplastic stroma of carcinomas [2].
• Endothelial cells and angiosarcomas showed multiple VLA-types: VLA1, 2, 3, 5, and 6 in a similar manner [2].
• Mesenchymal cell/tumor types had characteristic patterns of VLA integrins; for example, smooth muscle and its benign tumors showed VLA1, 3, and 5, whereas schwannomas showed VLA1, 2, 3 and 6 [2].
• The alpha1beta1 (VLA-1) integrin is a cell-surface receptor for collagen and laminin and has been implicated in biological pathways involved in several pathological processes [3].

High impact information on ITGA1

• Localization of matrix metalloproteinase MMP-2 to the surface of invasive cells by interaction with integrin alpha v beta 3 [4].
• Integrin alpha v beta 3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels [5].
• We demonstrate therefore that ligation of integrin alpha v beta 3 is required for the survival and maturation of newly forming blood vessels, an event essential for the proliferation of tumors [5].
• A single intravascular injection of a cyclic peptide or monoclonal antibody antagonist of integrin alpha v beta 3 disrupts ongoing angiogenesis on the chick chorioallantoic membrane (CAM) [5].
• Integrin alpha 2 beta 1 (VLA-2) mediates reorganization and contraction of collagen matrices by human cells [6].

Chemical compound and disease context of ITGA1

• Here we demonstrate that binding of B. burgdorferi to human platelets is mediated by the integrin alpha IIb beta 3 (glycoprotein IIb-IIIa), a critical receptor in thrombosis and hemostasis [7].
• These data suggest that the expression of integrin alpha subunits can be regulated differentially and independently of the beta subunit and that the VLA-1 heterodimer has an important function in mediating Arg-Gly-Asp-dependent cell adhesion or other phenotypic properties in human neuroblastoma cells [8].
• Integrin alpha v beta 3 antagonist Cilengitide enhances efficacy of radiotherapy in endothelial cell and non-small-cell lung cancer models [9].
• Up-regulation of the integrin alpha 1/beta 1 in human neuroblastoma cells differentiated by retinoic acid: correlation with increased neurite outgrowth response to laminin [10].

Biological context of ITGA1

• Cell adhesion was dependent on extracellular divalent cations, a characteristic event of VLA-1 never before shown for IELs: manganese and magnesium ions supported binding in a dose-dependent manner; calcium ions inhibited their effectiveness [11].
• Human smooth muscle VLA-1 integrin: purification, substrate specificity, localization in aorta, and expression during development [12].
• By the 24th wk of gestation, the amount of VLA-1 integrin was significantly reduced in the aortic media (4.3-fold for alpha 1 subunit and 2.5-fold for beta 1 subunit) compared with that in the 10-wk-old aortic smooth muscle cells [12].
• To test this hypothesis, we have produced point mutations in the human integrin alpha 1 subunit [13].
• In this study the expression of early activation antigen, interleukin-2 receptor was compared with the expression of late activation antigens, HLA-DR, HLA-DP, and HLA-DQ molecules of the major histocompatibility complex II, and very late activation antigen, VLA-1 of the integrin superfamily of molecules in 43 human endometria [14].

Anatomical context of ITGA1

• Despite changes in the adhesive properties, there was essentially no difference in the expression of VLA-1, -3, -4, -5, and -6 between resting and stimulated T cells [15].
• Integrin alpha1beta1 (VLA-1) mediates adhesion of activated intraepithelial lymphocytes to collagen [11].
• The endothelium of the synovial vasculature stained intensely for beta 1, VLA-1, VLA-3 and VLA-5 with more limited staining for VLA-2 [16].
• VLA-1, VLA-2 and VLA-3 were present in glandular epithelium, stromal cells and vessels of both groups [17].
• The distribution of lymphocyte subsets and the beta 1 integrins (beta 1, VLA-1, 2, 3, 4, 5) were studied in 10 rheumatoid synovial membranes using immunohistochemistry and monoclonal antibodies [16].

Associations of ITGA1 with chemical compounds

• Expression of CD49a, CD49f, and alphad integrin was never detectable during CHMC differentiation [18].
• Binding study with the purified Aup1 and various glutathione S-transferase-alpha(IIb) cytoplasmic tail peptides revealed specific binding of Aup1 to the membrane-proximal sequence (KVGFFKR) that is conserved among the integrin alpha subunits and plays a crucial role in the alpha(IIb)beta(3) inside-out signaling [19].
• The studies described in this article characterize novel regulation of pp125FAK by the T cell receptor (TCR)-CD3 antigen complex and beta 1 integrins, and provide the first account, in any cell type, of integrin alpha 4 beta 1-mediated pp125FAK tyrosine phosphorylation [20].
• In particular, the alpha 2 sequence matched other integrin alpha chains in (a) the positions of 17 of its 20 cysteine residues; (b) the presence of three metal-binding domains of the general structure DXDXDGXXD; and (c) the transmembrane domain sequence [21].
• By immunoelectron microscopy VLA-1, VLA-6, beta1, and laminin were distributed throughout endothelial cells; alpha(v) was adjacent to and on luminal surfaces; alpha(v) and VLA-1 were on intercellular junctions [22].

Physical interactions of ITGA1

• Ancient ubiquitous protein 1 binds to the conserved membrane-proximal sequence of the cytoplasmic tail of the integrin alpha subunits that plays a crucial role in the inside-out signaling of alpha IIbbeta 3 [19].
• Cross-linking experiments showed that the VLA-1 complex is a heterodimer composed of an Mr 210,000 subunit (alpha 1) in acid-labile association with an Mr 130,000 subunit (beta) [23].
• Immunoprecipitation with anti-integrin alpha 2 antibodies or anti-integrin beta 1 antibody resulted in preferential coprecipitation of EGFR from A431 cell lysates, while anti-EGFR antibody coprecipitated integrin alpha 2 beta 1 [24].
• Finally, IRS-1 in LNCaP cells co-immunoprecipitates with integrin alpha 5 beta 1, and the association is again IGF-I-independent [25].
• Thus, the alpha(9) and alpha(4) integrin subunits form a paxillin-binding subfamily of integrin alpha subunits, and direct binding of paxillin to the alpha(9) cytoplasmic domain mediates some of the biological activities of the alpha(9)beta(1) integrin [26].

Co-localisations of ITGA1

• Integrin alpha-chains colocalized with talin, dependent on the matrix substrate [27].
• Unexpectedly, in these cells, TGN38 colocalizes with integrin alpha 5 beta 1 at the Golgi, the cell surface or in the footprints and an increased amount of both integrin subunits on the plasma membrane was observed [28].

Regulatory relationships of ITGA1

• Nodal follicular center cell lymphomas (FCCL) were VLA-1- and -2- and very rarely expressed VLA-5 and -6 [29].
• In the peripheral blood, patients with active rheumatoid arthritis expressed VLA-1 on 11.7 +/- 6.0% of their mononuclear cells, compared to 1.9 +/- 1.5% in controls (P less than 0.001) [30].
• The integrin alpha 4 beta 1 can provide a costimulus to induce IL-2 secretion and IL-2R expression leading to enhanced proliferation of purified, peripheral blood T cells [31].
• Talin controls the exit of the integrin alpha 5 beta 1 from an early compartment of the secretory pathway [32].
• In chronic inactive lesions beta1, VLA-6 and alpha(v) were the same as controls but VLA-1 remained increased [22].

Other interactions of ITGA1

• Cells in the synovial lining layer expressed beta 1, VLA-1, VLA-3 and and VLA-5 [16].
• Integrin alpha 1 (ITGA1) and WNT5A were also overexpressed [33].
• VLA-1 to VLA-6 are cell-surface molecules binding to matrix molecules such as collagen, fibronectin, epiligrin, and laminin [29].
• Unlike other integrin alpha subunits, the alpha subunit of VLA4 (alpha 4) can appear as a 150-kDa polypeptide (alpha 150), or cleaved into two non-covalently associated polypeptides (alpha 70-80) [34].
• Furthermore, patient derived T cells actively transmigrated through a collagen IV gel toward medium containing TNF-a, in a process that was inhibited by MAbs to VLA-1 [35].

Analytical, diagnostic and therapeutic context of ITGA1

• The complex was identified as VLA-1 integrin and consisted of two subunits of 195 and 130 kD in SDS-PAGE [12].
• We report here the molecular cloning of cDNAs encoding for the human integrin alpha 1 subunit [36].
• Subsequent yeast two-hybrid assay indicated binding of Aup1 to cytoplasmic tails of other integrin alpha subunits [19].
• Sequence analysis of PCR-amplified platelet GPIIb mRNA revealed an Arg327-->His amino acid substitution between the second and third calcium-binding domains of the GPIIb heavy chain, a residue that is highly conserved among integrin alpha-subunits [37].
• The specificity of 12F1 for VLA-2 allowed independent immunoprecipitation and flow cytometry analysis of this alpha 2 beta structure separate from any other VLA structures that may have been present such as VLA-1 or free beta-subunit [38].

References