Disease relevance of Olfr66

• BACKGROUND/AIMS: Following malignant transformation, epithelial cells of colorectal carcinomas, unlike normal colonic epithelial cells, no longer express the alpha 5 beta 1 fibronectin receptor [1].
• In an analysis of benign and malignant skin tumors induced by chemical carcinogens or oncogene transduction, we found that alpha 3 beta 1 and alpha 5 beta 1 as well as the non-integrin 67LR are sequentially down-regulated in the progression from benign to malignant, while alpha 6 beta 4 is the predominant receptor expressed in the carcinomas [2].
• B-cell lines functionally expressing alpha 5 beta 1 at high or moderate levels disseminated in SCID mice while alpha 5-negative lines and Daudi did not [3].
• These results support the conclusion drawn from an earlier in situ analysis of human B-cell lymphomas/leukemias that the alpha 5 beta 1 integrin contributes to the disseminative phenotype of malignant B cells [3].
• Invalpha 5 beta1 mice developed threefold more papillomas and squamous cell carcinomas than wild-type (Wt) littermates; however, no spindle cell tumors or increased metastases were observed [4].

High impact information on Olfr66

• We report here on gene transfer studies designed to investigate the function of the alpha 5 beta 1 integrin and its role in transformation [5].
• Elevated levels of the alpha 5 beta 1 fibronectin receptor suppress the transformed phenotype of Chinese hamster ovary cells [5].
• The pulmonary alveolar proteinosis in granulocyte macrophage colony-stimulating factor/interleukins 3/5 beta c receptor-deficient mice is reversed by bone marrow transplantation [6].
• The presence of GRGDS peptide allowed alpha 5 beta 1A to locate to focal contacts of GD25-beta 1A cultured on fibronectin, while the beta 1-null GD25 cells were unable to attach under these conditions [7].
• These data suggest that alpha 5 beta 1, alpha v beta 6, and alpha v beta 5, not routinely used by keratinocytes resting on an intact basement membrane, act as "emergency" receptors, and uncover at least one of the molecular mechanisms responsible for the peculiar integrin expression in healing human wounds [8].

Chemical compound and disease context of Olfr66

• Because in the antigen-stimulated acute infection spleen or granuloma cultures the co-stimulatory effect by FN was abrogated by the tripeptide (RGD) arg-gly asp, and anti alpha 5 beta 1 antibody, enhancement is attributed to signalling via the alpha 5 beta 1 integrin receptor of lymphocytes [9].
• Current investigations have indicated that the 5 beta steroid metabolites of testosterone are haematopoietic without the complication of virilization [10].

Biological context of Olfr66

• This indicates that the alpha-chains appear to determine whether an integrin cycles or not, and that alpha 5 beta 1, alpha 6 beta 4 and Mac-1 can be brought to the leading edge of a moving cell by endocytosis and recycling [11].
• Alpha 5 beta 1 integrin activates an NF-kappa B-dependent program of gene expression important for angiogenesis and inflammation [12].
• 12(S)-HETE-enhanced tumor cell adhesion was blocked by treating endothelial cells with antibodies against the alpha v beta 3 complex or against individual subunits but not with antibodies against alpha 5 beta 1 [13].
• Role of alpha 5 beta 1 integrin in TGF-beta 1-costimulated CD8+ T cell growth and apoptosis [14].
• Corticosterone, 5alpha-tetrahydrocorticosterone (5alphaTHB), and 5alpha-dihydrocorticosterone (5alphaDHB) were similarly effective in displacing tritiated dexamethasone from binding sites in hepatocytes, whereas 5beta-reduced metabolites were less effective in binding [15].

Anatomical context of Olfr66

• The alpha 5 beta 1 expressed by the erythroleukemic cell line K562 binds soluble fibronectin with low affinity (Kd > 1 microM), but is induced to bind it with 20-fold higher affinity (Kd-54 nM) in the presence of the anti-beta 1 mAb 8A2 [16].
• In contrast, alpha 5 beta 1 is primarily enriched at the cell-cell borders, demonstrating codistribution with cell cortical microfilaments and extracellular fibronectin [17].
• Macrophage-colony-stimulating factor regulates expression of the integrins alpha 4 beta 1 and alpha 5 beta 1 by murine bone marrow macrophages [18].
• GeneCalling, a genome-wide method of mRNA profiling, reveals that endothelial cells adhering to fibronectin through the alpha 5 beta 1 integrin, but not to laminin through the alpha 2 beta 1 integrin, undergo a complex program of gene expression [12].
• The alpha 5-null embryos have pronounced defects in posterior trunk and yolk sac mesodermal structures, suggesting a role for alpha 5 beta 1 integrin in mesoderm formation, movement or function [19].

Associations of Olfr66 with chemical compounds

• The role of EC integrins alpha v beta 3 and alpha 5 beta 1 in 12(S)-HETE induced EC retraction was investigated [17].
• The most evolved mutant is able to discriminate against 5beta- or 5alpha-dihydroprogesterone, 23 and 15 times better than the starting antibody, while maintaining the affinity for progesterone that remains in the picomolar range [20].
• When liposomes included a moderate quantity of GM3 (0.22-0.44 micrograms (0.2-0.4 nmol)/55 micrograms of phosphatidylcholine, 33 micrograms of cholesterol, 5 micrograms of alpha 5 beta 1 in liposome), adhesion was enhanced significantly [21].
• Variants selected by an initial screening in competition against a large excess of 5beta- or 5alpha-dihydroprogesterone were characterized by a convergent amino acid signature different from that of the wild-type antibody and had lower cross-reactivity [20].
• We expressed in cultured cells recombinant gamma-aminobutyric acid type A (GABAA) receptors of the subunit compositions alpha 1 beta j gamma k and alpha 5 beta j gamma k (j = 1, 2, or 3 and k = 2 or 3) [22].

Regulatory relationships of Olfr66

• Suprabasal alpha 5 beta1 integrin expression stimulates formation of epidermal squamous cell carcinomas without disrupting TGFbeta signaling or inducing spindle cell tumors [4].
• These results indicate that alpha 4 beta 1 function in these cells is suppressed in the presence of alpha 5 beta 1 [23].

Other interactions of Olfr66

• However, the embryos progress significantly further than embryos null for fibronectin, for which alpha 5 beta 1 integrin is a receptor, suggesting the involvement of other fibronectin receptors [19].
• Recent findings have also revealed heterophilic interactions between L1 and two "classical" integrin matrix receptors, murine alpha 5 beta 1 and human alpha V beta 3 [24].
• We report that a beta 1 integrin (alpha 5 beta 1) can exist in different affinity states for its soluble ligand, fibronectin [16].
• The alpha 5 beta 1, alpha 6 beta 4 and Mac-1 integrins all participate in the endocytotic cycle [11].
• In short term adhesion assays, the GlcNAc-TV expressing cells were less adhesive on surfaces coated with fibronectin and collagen type IV, but no changes were observed in levels of cell surface alpha 5 beta 1 or alpha v beta 3 integrins [25].

Analytical, diagnostic and therapeutic context of Olfr66

• Surprisingly, ligation of alpha 5 beta 1 on these cells by cell attachment to a fibronectin substrate not only reverses the growth inhibition and gas-1 gene induction but activates immediate early gene transcription [26].
• Immunoblotting and immunomorphological findings in the cultures treated with anti-beta 1 antibody from day 1 to day 3 revealed a pattern of integrins and collagen composed of beta 1, alpha 1, alpha 5 beta 1 integrins and collagen type I. The cartilage-specific chondroitin sulfate proteoglycan (CSPG) could not be demonstrated in these cultures [27].
• Properties of expressed recombinant alpha 5 beta X gamma 2L (where X = 1,2, or 3) GABARs were studied with the use of whole-cell, patch-clamp techniques [28].
• As determined by immunofluorescence flow cytometry assay, both a-EAT and na-EAT cells express similar amounts of surface antigen(s) recognized by the same anti-alpha 5 beta 1 integrin polyclonal antibody that blocks a-EAT cells from adhering to laminin and fibronectin [29].
• Localization and dynamic aspects of fibronectin receptor (alpha 5 beta 1 integrin) were investigated by immunoelectron microscopy on freshly isolated mouse peritoneal macrophages and after cultivation in vitro [30].

References