Disease relevance of Itga1

• Integrin alpha E beta 7 expression on BAL CD4+, CD8+, and gamma delta T-cells in bleomycin-induced lung fibrosis in mouse [1].
• Control of thrombus embolization and fibronectin internalization by integrin alpha IIb beta 3 engagement of the fibrinogen gamma chain [2].
• Polyclonal antibodies to the avian integrin alpha 1-subunit block attachment of embryonic gizzard cells to human and chick collagen IV completely and inhibit attachment to mouse Engelbreth-Holm-Swarm (EHS) tumor laminin partially [3].
• Phenotypic properties of cultured tumor cells: integrin alpha IIb beta 3 expression, tumor-cell-induced platelet aggregation, and tumor-cell adhesion to endothelium as important parameters of experimental metastasis [4].
• The lipoxygenase metabolite 12(S)-HETE induces a cytoskeleton-dependent increase in surface expression of integrin alpha IIb beta 3 on melanoma cells [5].

High impact information on Itga1

• Caveolin-1 functions as a membrane adaptor to link the integrin alpha subunit to the tyrosine kinase Fyn [6].
• Coimmunoprecipitation and mutagenesis experiments indicate that the recruitment of Shc is specified by the extracellular or transmembrane domain of integrin alpha subunit and suggest that this process is mediated by caveolin [7].
• Moreover, both ADP-dependent platelet aggregation and the activation of the integrin alpha IIb beta 3 (GPIIb-IIIa) were strongly reduced in platelets from G alpha(i2)-deficient mice [8].
• Primary megakaryocytes reveal a role for transcription factor NF-E2 in integrin alpha IIb beta 3 signaling [9].
• H36-alpha 7 is a novel integrin alpha chain that is developmentally regulated during skeletal myogenesis [10].

Biological context of Itga1

• Deletion of integrin alpha 1 by homologous recombination permits normal murine development but gives rise to a specific deficit in cell adhesion [11].
• Integrin alpha 1 is a receptor for laminin and collagen which is expressed widely and dynamically in embryogenesis and has been implicated in various developmental processes including establishment of the placenta and formation of the central and peripheral nervous system [11].
• Genetic mapping of the integrin alpha 1 gene (Vla1) to mouse chromosome 13 [12].
• We have used an interspecies backcross gene-mapping technique to map the Vla1 gene to the distal end of chromosome 13 in the mouse genome [12].
• The location of these residues accounts for the binding specificity of LFA-1-blocking antibodies and identifies particular conserved sequences (residues 126-150) in the I domain of CD11a and homologous sequences in other beta 2-integrin alpha subunits that may be important for ligand binding [13].

Anatomical context of Itga1

• Cytofluorometric analysis and immunoprecipitation showed that the alpha 2 subunit is an abundant integrin alpha subunit in the endothelial cells and that the alpha subunits associated with laminin binding in other types of cells are expressed in these cells only at low levels [14].
• Mucosal T lymphocyte numbers are selectively reduced in integrin alpha E (CD103)-deficient mice [15].
• The mucosal lymphocyte integrin alpha E(CD103)beta 7 is thought to be important for intraepithelial lymphocyte (IEL) localization or function [15].
• Native EHS laminin uses integrin alpha 1 beta 1 for hepatocyte binding to the center of the cross (fragment P1) and other beta 1 integrin(s) in addition to alpha 1 beta 1 as receptors for the distal part of the long arm (fragment E8) [16].
• As beta1 integrins are a major class of receptors for basal lamina components, we stained muscles with antibodies to the 10 integrin alpha subunits known to form dimers with beta1, to determine if any of these molecules were concentrated at synaptic sites on muscle fibers [17].

Associations of Itga1 with chemical compounds

• Integrin alpha 1 beta 1 is a collagen receptor expressed on many mesenchymal cells, but mice deficient in alpha 1 integrin (alpha1-KO) have no gross structural defects [18].
• Adhesion of human skin fibroblasts to Cyr61 is mediated through integrin alpha 6beta 1 and cell surface heparan sulfate proteoglycans [19].
• Binding to laminin-1 was abolished by EDTA and could be specifically inhibited by antibodies to the respective integrin alpha subunit [20].
• In the airways, where type IV collagen is abundant, but not the spleen, the CD49a(+) CD8 cells had reduced proportions of annexin V and caspase 8, and >80% expressed the TNF-alpha receptor II, while Fas, TNFR-I, and CD27 expression were similar to CD49a(-) cells [21].

Physical interactions of Itga1

• CD4, CD8, and gamma delta T-cells located in the epithelium express the integrin alpha E beta 7 that binds to E-cadherin on the epithelium [1].

Regulatory relationships of Itga1

• Control of myeloid-specific integrin alpha Mbeta 2 (CD11b/CD18) expression by cytokines is regulated by Stat3-dependent activation of PU.1 [22].

Other interactions of Itga1

• The Vla1 locus is located 3.5 cM distal to Ctla-3 and 7.8 cM distal to Htrla [12].
• We cloned the murine integrin gene encoding alpha E, localized it to chromosome 11, and generated integrin alpha E-deficient mice [15].
• Integrin alpha 1 and integrin alpha 2, which map to the same general region, are possible candidate loci, based on their embryonic expression and cellular function [23].
• To further examine the role of the integrin alpha subunit in these signaling functions, we assessed the contribution of the alpha 6 cytoplasmic domain variants to the signaling properties of the alpha 6 beta 1 integrin using P388D1 cells that had been transfected with either the alpha 6A or the alpha 6B cDNA [24].
• While the functions of integrin alpha chain cytoplasmic domains are not understood, it is possible that they contribute to transferring signals to the cell interior, e.g., by delivering cytoskeleton organizing signals in response to integrin engagement with extracellular matrix ligands [25].

Analytical, diagnostic and therapeutic context of Itga1

• Sequence analysis of rat integrin alpha E1 and alpha E2 subunits: tissue expression reveals phenotypic similarities between intraepithelial lymphocytes and dendritic cells in lymph [26].
• Lung fibrosis was induced by a single intratracheal instillation of BLM (0.125 U.mouse-1), and bronchoalveolar lavage (BAL) T-cell subpopulations were examined at various time-points for the expression of the integrin alpha E beta 7 by flow cytometry [1].
• These findings demonstrate that integrin alpha 5 beta 1 expression in the absence of attachment to fibronectin activates a signaling pathway leading to decreased cellular proliferation and that ligation of this receptor with fibronectin reverses this signal, thereby contributing to the proliferation of transformed cells [27].
• Homology PCR is a powerful technique for the identification of known and novel integrin alpha and beta subunit cDNAs in cells from the lung and other organs [28].

References