Integrin alpha V explained

Integrin alpha-V is a protein that in humans is encoded by the ITGAV gene.^[1]

Function

ITGAV encodes integrin alpha chain V. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. Alpha V undergoes post-translational cleavage to yield disulfide-linked heavy and light chains, that combine with multiple integrin beta chains to form different integrins. Among the known associating beta chains (beta chains 1,3,5,6, and 8; ITGB1, ITGB3, ITGB5, ITGB6, and ITGB8), each can interact with extracellular matrix ligands; the alpha V beta 3 integrin, perhaps the most studied of these, is referred to as the Vitronectin receptor (VNR). In addition to adhesion, many integrins are known to facilitate signal transduction.^[2]

Alpha V class integrins

In mammals the integrins that include alpha-V are :

Name	Synonyms	Distribution	Ligands	-	αVβ1		neurological tumors	vitronectin fibrinogen	-	αVβ3	vitronectin receptor^[3]	activated endothelial cells, melanoma, glioblastoma	vitronectin, fibronectin, fibrinogen, osteopontin, Cyr61, thyroxine^[4] ^[5]	-	αVβ5		widespread, esp. fibroblasts, epithelial cells	vitronectin and adenovirus	-	αVβ6		proliferating epithelia, esp. lung and mammary gland	fibronectin TGFβ1+3	-	αVβ8		neural tissue; peripheral nerve	fibronectin TGFβ1+3

Clinical significance

Overexpression of the ITGAV gene is associated with progression and spread of colorectal cancer,^[6] and prostate cancer.^[7]

As a drug target

The mAbs intetumumab, and abituzumab target this protein which is found on some tumour cells.^[8]

See also

• Cluster of differentiation

Further reading

• Horton MA . The alpha v beta 3 integrin "vitronectin receptor" . The International Journal of Biochemistry & Cell Biology . 29 . 5 . 721–5 . May 1997 . 9251239 . 10.1016/S1357-2725(96)00155-0 .
• Porter JC, Hogg N . Integrins take partners: cross-talk between integrins and other membrane receptors . Trends in Cell Biology . 8 . 10 . 390–6 . October 1998 . 9789327 . 10.1016/S0962-8924(98)01344-0 .
• Sajid M, Stouffer GA . The role of alpha(v)beta3 integrins in vascular healing . Thrombosis and Haemostasis . 87 . 2 . 187–93 . February 2002 . 11858476 . 10.1055/s-0037-1612971. 76995133 .
• Cooper CR, Chay CH, Pienta KJ . The role of alpha(v)beta(3) in prostate cancer progression . Neoplasia . 4 . 3 . 191–4 . 2002 . 11988838 . 1531692 . 10.1038/sj.neo.7900224.
• Cacciari B, Spalluto G . Non peptidic alphavbeta3 antagonists: recent developments . Current Medicinal Chemistry . 12 . 1 . 51–70 . 2005 . 15638730 . 10.2174/0929867053363522 .
• University of Edinburgh . Hope for transplant patients as study finds key to organ scarring . ScienceDaily . 2013 . December 2, 2014 .

External links

• • ITGAV Info with links in the Cell Migration Gateway

Notes and References

1. Sosnoski DM, Emanuel BS, Hawkins AL, van Tuinen P, Ledbetter DH, Nussbaum RL, Kaos FT, Schwartz E, Phillips D, Bennett JS . Chromosomal localization of the genes for the vitronectin and fibronectin receptors alpha subunits and for platelet glycoproteins IIb and IIIa . The Journal of Clinical Investigation . 81 . 6 . 1993–8 . June 1988 . 2454952 . 442653 . 10.1172/JCI113548 .
2. Web site: Entrez Gene: ITGAV integrin, alpha V (vitronectin receptor, alpha polypeptide, antigen CD51).
3. Hermann P, Armant M, Brown E, Rubio M, Ishihara H, Ulrich D, Caspary RG, Lindberg FP, Armitage R, Maliszewski C, Delespesse G, Sarfati M . The vitronectin receptor and its associated CD47 molecule mediates proinflammatory cytokine synthesis in human monocytes by interaction with soluble CD23 . The Journal of Cell Biology . 144 . 4 . 767–75 . February 1999 . 10037797 . 2132927 . 10.1083/jcb.144.4.767 .
4. Bergh . JJ . Lin . HY . Lansing . L . Mohamed . SN . Davis . FB . Mousa . S . Davis . PJ . Integrin alphaVbeta3 contains a cell surface receptor site for thyroid hormone that is linked to activation of mitogen-activated protein kinase and induction of angiogenesis. . Endocrinology . July 2005 . 146 . 7 . 2864-71 . 10.1210/en.2005-0102 . 15802494.
5. Schmohl . KA . Han . Y . Tutter . M . Schwenk . N . Sarker . RSJ . Steiger . K . Ziegler . SI . Bartenstein . P . Nelson . PJ . Spitzweg . C . Integrin αvβ3-dependent thyroid hormone effects on tumour proliferation and vascularisation. . Endocrine-related cancer . December 2020 . 27 . 12 . 685-697 . 10.1530/ERC-20-0353 . 33112795.
6. 25275062 . 34 . 10 . Overexpression of the ITGAV gene is associated with progression and spread of colorectal cancer . 2014 . Anticancer Res . 5599–607 . Waisberg J, De Souza VL, Affonso Junior RJ, Silva SR, Denadai MV, Margeotto FB, De Souza CS, Matos D.
7. Cooper CR, Chay CH, Pienta KJ . The role of alpha(v)beta(3) in prostate cancer progression . Neoplasia . 4 . 3 . 191–4 . 2002 . 11988838 . 1531692 . 10.1038/sj.neo.7900224.
8. Élez E, Kocáková I, Höhler T, Martens UM, Bokemeyer C, Van Cutsem E, Melichar B, Smakal M, Csőszi T, Topuzov E, Orlova R, Tjulandin S, Rivera F, Straub J, Bruns R, Quaratino S, Tabernero J . Abituzumab combined with cetuximab plus irinotecan versus cetuximab plus irinotecan alone for patients with KRAS wild-type metastatic colorectal cancer: the randomised phase I/II POSEIDON trial . Annals of Oncology . 26 . 1 . 132–40 . January 2015 . 25319061 . 10.1093/annonc/mdu474 . free .