Disease relevance of Itgb5

• Enhanced pathological angiogenesis in mice lacking beta3 integrin or beta3 and beta5 integrins [1].
• Thus, tumor cell metastasis can be regulated by a functional cooperation between cytokine signaling events and the adhesion receptor alpha v beta 5 in a manner independent of tumor cell growth [2].
• Normal development, wound healing, and adenovirus susceptibility in beta5-deficient mice [3].
• Here, we investigate the involvement of beta3 and beta5 integrins in the development and progression of mammary carcinomas [4].
• We intercrossed mouse mammary tumor virus (MMTV)-c-neu transgenic mice with beta3 or beta5 or beta3beta5 integrin-deficient mice and observed that multiple, large mammary tumors developed in 100% of mice on all genetic backgrounds [4].

High impact information on Itgb5

• Polymerase chain reactions detected mRNAs for alpha 5, alpha 6, alpha v, beta 1, beta 3, and beta 5 [5].
• By contrast, we find that transgenic INS-I-E mice that express I-E on pancreatic beta-cells, but not in the thymus or peripheral lymphoid organs, are tolerant to I-E but have not deleted V beta 5- and V beta 17a-bearing T cells [6].
• T-cell reactivity to the class II major histocompatibility complex I-E antigen is associated with T-cell antigen receptors containing the V beta gene segments V beta 17a and V beta 5 [6].
• Rhythmic activation of focal adhesion and Mer tyrosine kinases that mediate wild-type retinal phagocytosis was also completely absent in beta5-/- retina [7].
• Here, we tested RPE phagocytosis and retinal function in beta5 integrin--deficient mice, which specifically lack alphavbeta5 receptors [7].

Chemical compound and disease context of Itgb5

• Undifferentiated epithelia express high levels of alpha v beta 5 integrins and are easily infected with recombinant adenoviruses; gene transfer is completely inhibited with excess fiber and partially inhibited with RGD peptide and alpha v beta 5 integrin antibody [8].

Biological context of Itgb5

• We have shown previously that oligodendrocyte precursors in vitro express a limited repertoire of integrins, including alpha 6 beta 1, alpha v beta 3, and that differentiation is associated with downregulation of alpha v beta 1 and upregulation of alpha v beta 5 [9].
• In summary, we have identified a 19-bp cis-element mediating GM-CSF-induced down-regulation of beta5 by a mechanism requiring protein synthesis [10].
• Expression of this construct in cultured human embryonic kidney cells under the control of the inducible metallothionein promoter resulted in cell rounding and detachment, and blocked cell adhesion mediated by the beta 1 and alpha v beta 5 integrins [11].
• Using deletion mutants, we localized a 109-base pair (bp) promoter region responsible for GM-CSF-inhibited beta5 transcription [10].
• A 13-kilobase (kb) genomic fragment containing part of the beta5 gene was isolated by screening a mouse genomic library with a probe derived from the most 5'-end of a murine beta5 cDNA [10].

Anatomical context of Itgb5

• On the other hand, the beta3 integrin mRNA was found only in large and round cells (presumptive germ cells), whereas beta5 integrin was localized in gonadal somatic cells, with the exception of coelomic epithelial cells [12].
• To examine the in vivo function of this receptor, we have generated mice lacking beta5 expression, using homologous recombination in embryonic stem cells [3].
• Keratinocytes harvested from beta5(-/-) mice demonstrate impaired migration on and adhesion to the alphavbeta5 ligand, vitronectin [3].
• We previously noted that the initial receptor by which murine osteoclast precursors bind matrix is the integrin alphav beta5 and that granulocyte-macrophage colony-stimulating factor (GM-CSF) decreases expression of this heterodimer by suppressing transcription of the beta5 gene [10].
• The groove is large enough to accommodate the loop between beta-strands beta4 and beta5 of the lectin domain of E-selectin that has been implicated in neutrophil adhesion (1) [13].

Associations of Itgb5 with chemical compounds

• Northern analysis demonstrates that cycloheximide treatment abrogates the capacity of GM-CSF to decrease beta5 mRNA levels [10].
• Mice lacking the integrin beta5 subunit have accelerated osteoclast maturation and increased activity in the estrogen-deficient state [14].
• A notable feature of the distribution of the beta 5 subunit in the glandular and luminal epithelium is its apical localization, which may suggest an involvement in implantation [15].
• The induction of migration was blocked by alpha v beta 5-specific antibodies and required Arg-Gly-Asp sites in L1 [16].
• Glra1 assembles into a pentameric complex with the beta subunit of the glycine receptor (3 alpha (1)2 beta 5) to form a glycine-gated chloride channel [17].

Regulatory relationships of Itgb5

• Expression of alpha v beta 5 in tumor cells promoted their adhesion to vitronectin in vitro [2].
• We propose that ectodomain-released L1 promotes migration by autocrine/paracrine stimulation via alpha v beta 5 [16].
• In C57BL/6 mice, most M-MuLV-specific CD8+ CTL clones and immune PBL coexpressed V alpha3.2 in association with V beta5 [18].
• The G protein beta5 expressed in transfected COS cells was properly folded as its pattern of stable C-terminal proteolytic fragments was identical to that of native brain beta5 [19].
• RGS/beta5 complexes may contribute to the selectivity of signal transduction initiated by receptors coupled to G(i) and G(o) by binding to phospholipase C and stimulating the GTPase activity of Galpha(o) [20].

Other interactions of Itgb5

• The expressions of integrin beta3, beta5, and beta6 were unaltered [21].
• Analysis of adhesive functions of transfected cells shows that beta1B interferes in a dominant negative manner with beta1A and beta3/beta5 integrins in cell spreading, focal adhesion formation, focal adhesion kinase tyrosine phosphorylation, and fibronectin matrix assembly [22].
• This subunit is known to associate with beta 5, and we therefore suggest that integrin alpha v beta 5 is involved in epithelial-mesenchymal interactions during tooth development [23].
• The RET phosphopeptide binds to Dok1 via a surface groove formed between strand beta5 and the C-terminal alpha-helix of the PTB domain [24].
• Transforming growth factor-beta up-regulates the beta 5 integrin subunit expression via Sp1 and Smad signaling [25].

Analytical, diagnostic and therapeutic context of Itgb5

• MATERIALS AND METHODS: Three-month-old wildtype (WT) and beta5(-/-) female mice had ovariectomy (OVX) or sham operations [14].
• We demonstrate the presence of integrin beta 5 polypeptide in human endometrial epithelial cells throughout the menstrual cycle using immunocytochemistry with monospecific antibodies, and at the mRNA level by thermal amplification from endometrial cDNA [15].
• Using in situ hybridization, the mRNA expression pattern of the beta 5 integrin receptor subunit was examined during murine tooth development, a classical system for studying morphogenesis [26].
• We report the beta5 gene expression pattern in embryonic and foetal mouse tissues as determined by Northern blotting and in situ hybridization [27].
• Southern blot analysis of liver DNA using TCR V beta-specific probes confirmed the deletion of V beta 8 gene subfamily and V beta 5 gene subfamily, along with V beta 9, V beta 11, V beta 12, and V beta 13 genes similar to the known TCR V beta deletion mutants (SWR, SJL, C57L, and C57Br) [28].

References