Disease relevance of ITGA2

• Genetic variants in the GP1BA and ITGA2 genes have been proposed as potential modifiers for arterial vascular disease and bleeding disorders [1].
• All tumors strongly positive for VLA2 or CD44 showed invasion beyond the renal capsule or metastases [2].
• In vivo distribution of integrins in renal cell carcinoma: integrin-phenotype alteration in different degrees of tumor differentiation and VLA-2 involvement in tumor metastasis [3].
• Platelets from the patients with Glanzmann's thrombasthenia could also attach to the subendothelium, whereas those from a patient whose platelets lacked GPIa failed to attach to the extracellular matrix (ECM) [4].
• The ITGA2 1648_AA genotype was significantly associated with breast cancer (odds ratio 3.12; 95% confidence interval 1.11-8.77) [5].

High impact information on ITGA2

• Targeted and natural (piebald-lethal) mutations of endothelin-B receptor gene produce megacolon associated with spotted coat color in mice [6].
• Integrin alpha 2 beta 1 (VLA-2) mediates reorganization and contraction of collagen matrices by human cells [7].
• Here we report the cloning and expression of a second human natriuretic peptide-receptor guanylate cyclase, the ANP-B receptor [8].
• In separate studies, the 'very late antigens' VLA-1 (Mr 210K/130K) and VLA-2 (Mr 160K/130K) were initially characterized as surface heterodimers appearing 2-4 weeks after in vitro stimulation of human T cells [9].
• RD rhabdomyosarcoma cells expressed little VLA-2, did not bind to 35S-labeled virus, and resisted infection until transfected with complementary DNA encoding the alpha 2 subunit of VLA-2 [10].

Chemical compound and disease context of ITGA2

• Our results suggest that VLA-2 integrin is involved in metastasis of RCC and that poorly differentiated tumor cells have a different integrin phenotype when compared to normal or highly differentiated tumor cells [3].
• Infection by SA-dependent or SA-independent rotavirus strains was 2- to 10-fold more productive in VLA-2-expressing CHO cells than in parental CHO cells, and the increased susceptibility to infection was blocked with anti-VLA-2 antibody [11].
• In non-neoplastic breast tissue and in fibroadenomas VLA-2 and VLA-3 were expressed by myoepithelial cells and on the basolateral surface of the luminal cells [12].
• Hypercholesterolemia and hypoalphalipoproteinemia (low HDL cholesterol levels) are apparently no major risk factors for SHL, whereas the GPIa C807T polymorphism, elevated fibrinogen levels, and smoking are associated with an increased risk for SHL [13].
• METHODS: One hundred fifty-eight patients with chronic renal insufficiency [mean serum creatinine +/- SD = 2.7 +/- 1.0 mg/dL (242. 3 to +/- 92.8 micromol/L)] and undergoing cardiac angiography were randomized to receive either a mixed endothelin A and B receptor antagonist, SB 290670, or placebo [14].

Biological context of ITGA2

• ITGA2 haplotype 2 (807C) and ITGA2B haplotype 1 (Ile(843)) were each associated with increased bleeding severity scores (P < .01 and P < .01, respectively) [15].
• Resolution of this discrepancy suggests that there may be another VLA heterodimer that resembles VLA-2 in size but has a different amino acid sequence [16].
• There were no differences in the genotype distribution and allele frequencies between bleeders and non bleeders for the platelet alloantigen systems HPA-1, 2, 5 and the GPIa C807T polymorphism [17].
• These results indicate that T-cell adherence to fibroblasts is enhanced by butyric acid and that butyric acid-induced T-cell apoptosis is down-regulated by T-cell adhesion to gingival fibroblasts through an interaction with the adhesion molecules CD44, VLA-2, and VLA-5 expressed on T cells stimulated with butyric acid [18].
• Hence, VLA-2 is not expressed on immature Mks but is present on the mature polyploid cells [19].

Anatomical context of ITGA2

• Studies with alpha-subunit (CD49)-specific mAbs indicated that the integrins VLA-4 and -5 mediated migration across FN-preincubated filters, and VLA-2, -4, -5, and -6 were involved in eosinophil migration through filters covered with HUVEC [20].
• As assessed by inhibition of adhesion using mAb to the VLA-2, -3, -4, -5, and -6, NK cell adhesion to fibronectin was mediated by VLA-4 and 5, and their adhesion to laminin by VLA-3 and -6 [21].
• VLA proteins such as VLA-4, VLA-3, or VLA-2, which are found involved in cell-cell contacts, could contribute to the promotion of T-cell activation by facilitating adherence between LC and T cells [22].
• Both in normal and EB specimens MoAb against VLA-2, VLA-3, and VNR alpha determinants showed reactivity with the total cytoplasmic membrane of basal keratinocytes and basement membrane zone [23].
• VLA-1, VLA-2 and VLA-3 were present in glandular epithelium, stromal cells and vessels of both groups [24].

Associations of ITGA2 with chemical compounds

• VLA-2 (also called gpIa/IIa on platelets) is a collagen receptor with a unique alpha subunit and a beta subunit common to other adhesion receptors in the VLA/integrin family [16].
• Further, the anti-GPIa antibody (Gi9) inhibited liposome adhesion more than GUR83-35 at all shear rates tested [25].
• After contact with polyethylene terephthalate, a slight but significant decrease in the percentage of both CD29 and CD49e positive cells was observed, which suggests a lower number of cells expressing the fibronectin receptor alpha5beta1 [26].
• PATIENTS AND METHODS: The glycoprotein alpha(IIb)beta3 (GPIIb/IIIa) is the main fibrinogen receptor on platelets, with GPIb-IX-V and GPIa/IIa being the von Willebrand Factor and collagen receptors, respectively [27].
• CONCLUSIONS: In vivo selection and flow cytometric analysis revealed that Lea, sLea, CD49b, CD49c, and CD29 appear to be involved in the increase of metastatic activity [28].

Physical interactions of ITGA2

• These data support a model wherein collagen can directly interact with GPIa/IIa and can indirectly interact with GPIIb/IIIa via intermediary adhesive proteins [29].
• The VLA-2 complex (alpha 2/beta 1) was found to act as collagen receptor on platelets and the VLA-6 complex (alpha 6/beta 1) as laminin receptor [30].
• Absolute values for lifetime and anisotropy were lower for the CCK-8 probe bound to the type B receptor than for this probe bound to the type A receptor, and Alexa fluorescence was more easily quenched by iodide at the type B receptor [31].

Regulatory relationships of ITGA2

• Peripheral monocytes from patients with IgA nephropathy expressed VLA-2 alpha, 4 alpha and 5 alpha, but not VLA-1 alpha or 3 alpha [32].
• Most of the potentiating effects (88%) were blocked by the ETA receptor antagonist LU135252 and slightly further blocked by the ETA/B receptor antagonist bosentan (P<0.05) [33].
• Immunoprecipitation experiments confirmed that the VLA-1 protein complex (210 000/130 000 Mr) can be co-expressed with another protein complex called VLA-2 (165 000/130 000 Mr) on the same T cell clones [34].

Other interactions of ITGA2

• IL-6 induced expression of CD49b (alpha-chain of VLA-2, 20% +/- 11 vs 2% +/- 1) and CD49c (alpha-chain of VLA-3, 43% +/- 17 vs 5% +/- 3), which are not expressed on resting NK cells [21].
• Using a panel of specific antibodies we showed that freshly harvested human epidermal basal cells express VLA-2 and VLA-3 receptors, a low amount of VLA-5, but fail to express VLA-4 [35].
• These results show that PltGPs HPA-1, 2 and 5 or the C807T dimorphism of GPIa do not influence the clinical expressivity of VWD type 1 [17].
• Moreover, a significant increase in the mean channel for CD49b and for the vitronectin receptor CD51/CD61 was observed [26].
• Our results show that only VLA-2, VLA-3, LFA-3, and the VLA-alpha 6 subunit are expressed on the epithelium [36].

Analytical, diagnostic and therapeutic context of ITGA2

• To analyze the role of ITGA2 and ITGB3 polymorphisms for breast cancer risk and prognosis, we performed a case-control study including 500 female breast cancer patients and 500 healthy female age-matched control subjects [5].
• To define the polymorphism responsible for the Br alloantigen system platelet RNA PCR technique, was used to amplify GPIa mRNA transcripts [37].
• Immunoprecipitation with specific monoclonal antibodies identified the complexes as very late activation antigen (VLA)-1 (alpha 1 beta 1) and VLA-2 (alpha 2 beta 1), respectively [38].
• Localization of the Br polymorphism on a 144 bp exon of the GPIa gene and its application in platelet DNA typing [39].
• A de novo expression of VLA-1, VLA-2, and VLA-4 as detected by immunocytochemistry occurred in resistant Caki-1 cells [40].

References