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Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
Integrins are unusual signalling proteins that function to signal both from the extracellular environment into the cell, but also from the cytoplasm to the external of the cell. The intracellular signalling cascades associated with integrin activation focus on protein kinase activities, such as focal adhesion kinase and Src. Based on this association between extracellular signals and intracellular protein kinase activity, we have chosen to include integrins in the ‘Catalytic receptors’ section of the database until more stringent criteria from NC-IUPHAR allows precise definition of their classification.
Integrins are heterodimeric entities, composed of α and β subunits, each 1TM proteins, which bind components of the extracellular matrix or counter-receptors expressed on other cells. One class of integrin contains an inserted domain (I) in its α subunit, and if present (in α1, α2, α10, α11, αD, αE, αL, αM and αX), this I domain contains the ligand binding site. All β subunits possess a similar I-like domain, which has the capacity to bind ligand, often recognising the RGD motif. The presence of an α subunit I domain precludes ligand binding through the β subunit. Integrins provide a link between ligand and the actin cytoskeleton (through typically short intracellular domains). Integrins bind several divalent cations, including a Mg2+ ion in the I or I-like domain that is essential for ligand binding. Other cation binding sites may regulate integrin activity or stabilise the 3D structure. Integrins regulate the activity of particular protein kinases, including focal adhesion kinase and integrin-linked kinase. Cellular activation regulates integrin ligand affinity via inside-out signalling and ligand binding to integrins can regulate cellular activity via outside-in signalling.
* Key recommended reading is highlighted with an asterisk
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Humphries JD, Byron A, Humphries MJ. (2006) Integrin ligands at a glance. J. Cell. Sci., 119 (Pt 19): 3901-3. [PMID:16988024]
* Hynes RO. (2002) Integrins: bidirectional, allosteric signaling machines. Cell, 110 (6): 673-87. [PMID:12297042]
* Ivaska J, Heino J. (2011) Cooperation between integrins and growth factor receptors in signaling and endocytosis. Annu. Rev. Cell Dev. Biol., 27: 291-320. [PMID:21663443]
Kim C, Ye F, Ginsberg MH. (2011) Regulation of integrin activation. Annu. Rev. Cell Dev. Biol., 27: 321-45. [PMID:21663444]
Roca-Cusachs P, Iskratsch T, Sheetz MP. (2012) Finding the weakest link: exploring integrin-mediated mechanical molecular pathways. J. Cell. Sci., 125 (Pt 13): 3025-38. [PMID:22797926]
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Database page citation:
Richard Farndale, Gavin Jarvis. Integrins. Accessed on 29/04/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=760.
Concise Guide to PHARMACOLOGY citation:
Alexander SPH, Fabbro D, Kelly E, Marrion N, Peters JA, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Southan C, Davies JA and CGTP Collaborators (2015) The Concise Guide to PHARMACOLOGY 2015/16: Catalytic receptors. Br J Pharmacol. 172: 5979-6023.