Integrin beta 8 explained

Integrin beta-8 is a protein that in humans is encoded by the ITGB8 gene.^[1]

Function

This gene is a member of the integrin beta chain family and encodes a single-pass type I membrane protein with a VWFA domain and four cysteine-rich repeats. This protein noncovalently binds to an alpha subunit to form a heterodimeric integrin complex. In general, integrin complexes mediate cell-cell and cell-extracellular matrix interactions and this complex plays a role in human airway epithelial proliferation. Alternatively spliced variants which encode different protein isoforms have been described; however, not all the variants have been fully characterized.^[1] Additionally, it has been shown to interact with RhoGDI1 to alter the activation of Rho GTPases to promote Glioblastoma cell invasiveness. Uncoupling the αvβ8-RhoGDI1 interaction has been seen to block GBM cell invasion by hyperactivating Rho GTPases.^[2]

Clinical significance

High expression levels of ITGB8 are associated with high angiogenic and poorly invasive glioblastoma tumors. Conversely low expression of ITGB8 correlates with highly invasive but low angiogenic tumors.^[3]

Further reading

• Moyle M, Napier MA, McLean JW . Cloning and expression of a divergent integrin subunit beta 8. . J. Biol. Chem. . 266 . 29 . 19650–8 . 1991 . 10.1016/S0021-9258(18)55042-0 . 1918072 . free .
• Nishimura SL, Sheppard D, Pytela R . Integrin alpha v beta 8. Interaction with vitronectin and functional divergence of the beta 8 cytoplasmic domain. . J. Biol. Chem. . 269 . 46 . 28708–15 . 1994 . 10.1016/S0021-9258(19)61963-0 . 7525578 . free .
• Pilewski JM, Latoche JD, Arcasoy SM, Albelda SM . Expression of integrin cell adhesion receptors during human airway epithelial repair in vivo. . Am. J. Physiol. . 273 . 1 Pt 1 . L256–63 . 1997 . 9252563 . 10.1152/ajplung.1997.273.1.L256.
• Toward a complete human genome sequence. . Genome Res. . 8 . 11 . 1097–108 . 1999 . 9847074 . 10.1101/gr.8.11.1097. Sanger Centre . The . Washington University Genome Sequencing Cente . The . free .
• Cambier S, Mu DZ, O'Connell D, etal . A role for the integrin alphavbeta8 in the negative regulation of epithelial cell growth. . Cancer Res. . 60 . 24 . 7084–93 . 2001 . 11156415 .
• Mu D, Cambier S, Fjellbirkeland L, etal . The integrin αvβ8 mediates epithelial homeostasis through MT1-MMP–dependent activation of TGF-β1 . J. Cell Biol. . 157 . 3 . 493–507 . 2002 . 11970960 . 10.1083/jcb.200109100 . 2173277 .
• Jarad G, Wang B, Khan S, etal . Fas activation induces renal tubular epithelial cell beta 8 integrin expression and function in the absence of apoptosis . J. Biol. Chem. . 277 . 49 . 47826–33 . 2003 . 12324452 . 10.1074/jbc.M204901200 . free .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Scherer SW, Cheung J, MacDonald JR, etal . Human Chromosome 7: DNA Sequence and Biology . Science . 300 . 5620 . 767–72 . 2003 . 12690205 . 10.1126/science.1083423 . 2882961 . 2003Sci...300..767S .
• Hillier LW, Fulton RS, Fulton LA, etal . The DNA sequence of human chromosome 7 . Nature . 424 . 6945 . 157–64 . 2003 . 12853948 . 10.1038/nature01782 . 2003Natur.424..157H . free .
• Fjellbirkeland L, Cambier S, Broaddus VC, etal . Integrin αvβ8-Mediated Activation of Transforming Growth Factor-β Inhibits Human Airway Epithelial Proliferation in Intact Bronchial Tissue . Am. J. Pathol. . 163 . 2 . 533–42 . 2003 . 12875973 . 10.1016/S0002-9440(10)63681-4. 1868219 .
• Rual JF, Venkatesan K, Hao T, etal . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .
• Yan W, Shao R . Transduction of a mesenchyme-specific gene periostin into 293T cells induces cell invasive activity through epithelial-mesenchymal transformation . J. Biol. Chem. . 281 . 28 . 19700–8 . 2006 . 16702213 . 10.1074/jbc.M601856200 . free .

External links

• ITGB8 Info with links in the Cell Migration Gateway

Notes and References

1. Web site: Entrez Gene: ITGB8 integrin, beta 8.
2. Reyes SB, Narayanan AS, Lee HS, Tchaicha JH, Aldape KD, Lang FF, Tolias KF, McCarty JH . αvβ8 Integrin Interacts with RhoGDI1 to Regulate Rac1 and Cdc42 Activation and Drive Glioblastoma Cell Invasion . Mol Biol Cell . January 2012 . 23283986 . 10.1091/mbc.E12-07-0521 . 24 . 4 . 474–82. 3571870 .
3. Tchaicha JH, Reyes SB, Shin J, Hossain MG, Lang FF, McCarty JH . Glioblastoma Angiogenesis and Tumor Cell Invasiveness Are Differentially Regulated by 8 Integrin . Cancer Res. . 71 . 20 . 6371–81 . October 2011 . 21859829 . 10.1158/0008-5472.CAN-11-0991 . 3193578.