Disease relevance of Itga3

• Podocyte migration during nephrotic syndrome requires a coordinated interplay between cathepsin L and alpha3 integrin [1].
• Tumor cell adhesion (melanoma, ovarian carcinoma) to the alpha 1(IV)531-543 chemically synthesized peptide was inhibited by a monoclonal antibody against the alpha 3 integrin subunit, and to a lesser extent by monoclonal antibodies against the beta 1 and alpha 2 integrin subunits [2].
• Flow cytometric analysis of a panel of human colon carcinoma cell lines obtained from blood group A, AB, or B individuals revealed a direct correlation between cell-surface expression of the 3A7 epitope and alpha3 integrin subunit, suggesting that alpha3beta1 integrin is a preferred target of the 3A7 epitope in colon cancer cells [3].
• Proteins detected by antibodies to beta 4 integrin and alpha 3 integrin were also cleaved by the HIV-1 PR [4].
• Identification of a TLR-independent pathway for Borrelia burgdorferi-induced expression of matrix metalloproteinases and inflammatory mediators through binding to integrin alpha 3 beta 1 [5].

High impact information on Itga3

• Importantly, phosphorylation at those sites regulates alpha3 integrin levels, which is critical for the timely detachment of migrating neurons from radial glia [6].
• Using antibodies to podocyte proteins important for podocyte function, we found that Lmx1b(-/-) podocytes express near-normal levels of nephrin, synaptopodin, ZO-1, alpha3 integrin, and GBM laminins [7].
• Furthermore, the targeted mutation of the alpha3 integrin gene results in abnormal layering of the cerebral cortex [8].
• Because we detected reelin, alpha3-integrin receptor subunits, and disabled-1 immunoreactivity in HNSC cultures, it is possible that integrin-mediated reelin signal transduction is operative in these cultures [9].
• Calbindin or calretinin positive upper layer neurons as well as the deep layer neurons of alpha3 integrin mutant mice expressing EGFP were misplaced [10].

Chemical compound and disease context of Itga3

• NCAM and integrin alpha 3 expressed on the surface of SW480 cells were lost from metastatic cells, while carbohydrate ligands sialyl Lewis x and a, previously shown to be upregulated in metastatic colorectal tumors, were expressed at higher levels on colonizing cells [11].

Biological context of Itga3

• In the current study, we exploited keratinocyte cell lines derived from wild-type or alpha 3 integrin knockout mice to reveal a critical role for alpha 3 beta 1 in protecting keratinocytes from apoptosis upon serum withdrawal [12].
• In a search for key regulators of salivary cell lineage, we have studied alpha3beta1 integrin, a receptor for the basement membrane protein laminin, by characterizing embryonic day 18 (E18) SMGs isolated from mice carrying a targeted mutation in the alpha3 integrin gene [13].
• The murine alpha 3 integrin gene was found to contain a CCAAT box, but to lack a TATA box [14].
• Mice with genetically reduced expression of alpha3 integrin fail to maintain long-term potentiation (LTP) generated in hippocampal CA1 neurons [15].
• In contrast one of the blocking monoclonal antibodies against the alpha 3-integrin subunit (P1B5) mimicked the effect of soluble 'morphogens'. Our results suggest that the modulation of alpha 3 beta 1 activity may represent an important event in the induction of branching morphogenesis of human mammary epithelial cells [16].

Anatomical context of Itga3

• Examination of the actin cytoskeleton of alpha3 integrin mutant cortical cells reveals aberrant actin cytoskeletal dynamics at the leading edges [10].
• SCF down-regulated expression of alpha 2, alpha 5 and beta 1 integrins by fetal melanocytes, and up-regulated expression of the alpha v and alpha 3 integrin receptors [17].
• However, in cultures from alpha3 integrin-deficient mice, alpha6 beta1 mediates retinal ganglion cell neurite outgrowth and compensates for the absence of alpha3 beta1 [18].
• Proliferation of human epithelial cells is significantly inhibited by a function-perturbing alpha3 integrin antibody [19].
• Flow cytometric analysis of Chinese hamster ovary (CHO) cells expressing different human integrin chains revealed that MAbs 7A8 and 7B11 detect the alpha3 integrin subunit whereas MAbs 8C7 and 8H7 detect the beta1 integrin subunit [3].

Associations of Itga3 with chemical compounds

• Using alpha3 integrin null eggs, we found that the alpha3beta1 integrin was not essential for sperm-egg binding and fusion [20].
• The association of transferrin receptor and integrin alpha 3 was apparently not the result of spurious disulphide-bond formation occurring during the protein purification, as iodoacetamide and GSH did not block the formation of the complex [21].
• The receptor for the basement membrane glycoprotein entactin is the integrin alpha 3/beta 1 [22].
• The integrin alpha 3 beta 1, which has been identified as a receptor for kalinin but not for laminin, is strongly expressed in RAC-11P/SD cells and it seems likely that this integrin is responsible for spreading of cells on kalinin [23].
• These results show that retinoic acid treatment alters the amounts of alpha 5 and alpha 3 integrin subunits during the F9 to RA phenotypic switch [24].

Regulatory relationships of Itga3

• These results suggest that the Sp3 and Ets transcription factors cooperatively regulate alpha3 integrin gene expression and that the contribution of each element depends on the type of tumor cells [25].

Other interactions of Itga3

• Protein sequence analysis revealed that p225 consists of two polypeptides, namely integrin alpha 3 heavy chain (approximately 130 kDa) disulphide-bonded to a monomer of the transferrin receptor (approximately 95 kDa) instead of the typical alpha 3 light chain (approximately 25 kDa) [21].
• These changes in laminin mRNAs were parallel with its receptors such as integrin alpha 3 and alpha 6 [26].
• Other known components of the pathway include members of the lipoprotein receptor family, the intracellular adaptor Dab1, and possibly integrin alpha 3 beta 1 [27].
• After a 5-day culture period the number of fibroblast-like cells with alpha 1-, alpha v- and alpha 5 beta 1-integrins had increased. alpha 3-integrin was hardly recognizable on these cells [28].

Analytical, diagnostic and therapeutic context of Itga3

• Immunoprecipitation studies of untreated or LEO101-treated cells indicate that the expression of the alpha 3 integrin, but not other integrins, was decreased by LEO101 [29].
• Indirect immunofluorescence microscopy of wounded BxPC-3 cells suggested a rapid endocytosis of alpha 3 integrin subunit in the cells at the margin of the wound and a rapid, polarized rearrangement of the alpha 6 beta 4 integrin [30].
• Near-infrared optical imaging of ovarian cancer xenografts with novel alpha 3-integrin binding peptide "OA02" [31].

References