View source for Integrin

{{Pfam box
| Symbol = Integrin_alphaVbeta3
| Name = Integrin alphavbeta3 extracellular domains
| width =
| caption = Structure of the extracellular segment of integrin alpha Vbeta3.<ref name="pmid11546839">{{cite journal |author=Xiong JP, Stehle T, Diefenbach B, ''et al.'' |title=Crystal structure of the extracellular segment of integrin alpha Vbeta3 |journal=Science |volume=294 |issue=5541 |pages=339–45 |date=October 2001 |pmid=11546839 |pmc=2885948 |doi=10.1126/science.1064535 |url=}}</ref>
| Pfam = PF08441
| Pfam_clan = CL0159
| InterPro = IPR013649
| SMART =
| PROSITE =
| SCOP = 1jv2
| TCDB =
| OPM family =
| OPM protein =
| PDB = {{PDB2|1jv2}}, {{PDB2|1l5g}}, {{PDB2|1m1x}}, {{PDB2|1u8c}}
}}
{{Pfam box
| Symbol = Integrin_alpha
| Name = Integrin alpha cytoplasmic region
| width =
| caption = Structure of chaperone protein PAPD.<ref name="pmid10446050">{{cite journal |author=Sauer FG, Fütterer K, Pinkner JS, Dodson KW, Hultgren SJ, Waksman G |title=Structural basis of chaperone function and pilus biogenesis |journal=Science |volume=285 |issue=5430 |pages=1058–61 |date=August 1999 |pmid=10446050 |doi= 10.1126/science.285.5430.1058|url=}}</ref>
| Pfam = PF00357
| InterPro = IPR000413
| SMART =
| PROSITE = PDOC00215
| SCOP = 1dpk
| TCDB =
| OPM family = 197
| OPM protein = 2knc
| PDB = {{PDB2|1dpk}}, {{PDB2|1dpq}}, {{PDB2|1kup}}, {{PDB2|1kuz}}, {{PDB2|1m8o}}, {{PDB2|1s4w}}
}}
{{Pfam box
| Symbol = Integrin_beta
| Name = Integrin, beta chain
| width =
| caption =
| Pfam = PF00362
| InterPro = IPR002369
| SMART = SM00187
| PROSITE = PDOC00216
| SCOP = 1jv2
| TCDB =
| OPM family =
| OPM protein =
| PDB = {{PDB2|1jv2}}, {{PDB2|1kup}}, {{PDB2|1kuz}}, {{PDB2|1l3y}}, {{PDB2|1l5g}}, {{PDB2|1m1x}}, {{PDB2|1m8o}}, {{PDB2|1s4x}}, {{PDB2|1txv}}, {{PDB2|1ty3}}, {{PDB2|1ty5}}, {{PDB2|1ty6}}, {{PDB2|1ty7}}, {{PDB2|1tye}}, {{PDB2|1u8c}}
}}
__NOTOC__
{{SI}}
{{CMG}}

==Overview==

'''Integrins''' are [[transmembrane receptors]] that mediate the attachment between a [[cell (biology)|cell]] and its surroundings, such as other cells or the [[extracellular matrix]] (ECM). In [[signal transduction]], integrins pass information about the chemical composition and mechanical status of the ECM into the cell. Therefore, in addition to transmitting mechanical forces across otherwise vulnerable membranes, they are involved in [[cell signaling]] and the regulation of [[cell cycle]], shape, and motility.

Typically, receptors inform a cell of the molecules in its environment and the cell responds. Not only do integrins perform this outside-in signaling, but they also operate an inside-out mode. Thus, they [[signal transduction|transduce]] information from the ECM to the cell as well as reveal the status of the cell to the outside, allowing rapid and flexible responses to changes in the environment, for example to allow blood [[coagulation]] by platelets.

There are many types of integrin, and many cells have multiple types on their surface. Integrins are of vital importance to all [[animal]]s and have been found in all animals investigated, from [[sponge]]s to [[mammal]]s. Integrins have been extensively studied in humans.

Integrins work alongside other [[protein]]s such as [[cadherin]]s, [[immunoglobulin superfamily]] [[cell adhesion molecule]]s, [[selectin]]s and [[syndecan]]s to mediate cell–cell and cell–matrix interaction and communication. Integrins bind cell surface and ECM components such as [[fibronectin]], [[vitronectin]], [[collagen]], and [[laminin]].

==Structure==

Integrins are [[obligate]] [[heterodimer]]s containing two distinct chains, called the α (alpha) and β (beta) subunits. In [[mammal]]s, eighteen α and eight β subunits have been characterized, whereas the ''[[Drosophila]]'' [[genome]] encodes only five α and two β subunits, and ''[[Caenorhabditis]]'' nematodes possess genes for two α subunits and one β.<ref name=hump>{{cite journal | author= Humphries M.J. | title= Integrin structure | journal=Biochem. Soc. Trans. | volume=28 | issue=4 |pages= 311–339 | year=2000 | pmid= 10961914 | doi = 10.1042/0300-5127:0280311}}</ref> The α and β subunits each penetrate the plasma membrane and possess small cytoplasmic domains.<ref name="pmid2977331">{{cite journal | author = Nermut MV, Green NM, Eason P, Yamada SS, Yamada KM | title = Electron microscopy and structural model of human fibronectin receptor | journal = EMBO J. | volume = 7 | issue = 13 | pages = 4093–9 |date=December 1988 | pmid = 2977331 | pmc = 455118 | doi = | url =  }}</ref>

{{Multicol|50%}}
'''alpha'''
{| class="wikitable" border="1" style="text-align:center"
|-
! gene
! protein
! synonyms are
|-
| {{gene|ITGA1}}
| [[CD49a]]
| VLA1
|-
| {{gene|ITGA2}}
| [[CD49b]]
| VLA2
|-
| {{gene|ITGA3}}
| [[CD49c]]
| VLA3
|-
| {{gene|ITGA4}}
| [[CD49d]]
| VLA4
|-
| {{gene|ITGA5}}
| [[CD49e]]
| VLA5
|-
| {{gene|ITGA6}}
| [[ITGA6|CD49f]]
| VLA6
|-
| {{gene|ITGA7}}
| [[ITGA7]]
| FLJ25220
|-
| {{gene|ITGA8}}
| [[ITGA8]]
|
|-
| {{gene|ITGA9}}
| [[ITGA9]]
| RLC
|-
| {{gene|ITGA10}}
| [[ITGA10]]
|
|-
| {{gene|ITGA11}}
| [[ITGA11]]
| HsT18964
|-
| {{gene|ITGAD}}
| [[ITGAD|CD11D]]
| FLJ39841
|-
| {{gene|ITGAE}}
| [[ITGAE|CD103]]
| HUMINAE
|-
| {{gene|ITGAL}}
| [[CD11a]]
| LFA1A
|-
| {{gene|ITGAM}}
| [[Integrin alpha M|CD11b]]
| MAC-1
|-
| {{gene|ITGAV}}
| [[ITGAV|CD51]]
| VNRA, MSK8
|-
| {{gene|ITGA2B}}
| [[ITGA2B|CD41]]
| GPIIb
|-
| {{gene|ITGAX}}
| [[CD11c]]
|
|}
{{Multicol-break}}
'''beta'''
{| class="wikitable" border="1" style="text-align:center"
|-
! gene
! protein
! synonyms
|-
| {{Gene|ITGB1}}
| [[CD29]]
| FNRB, MSK12, MDF2
|-
| {{Gene|ITGB2}}
| [[CD18]]
| LFA-1, MAC-1, MFI7
|-
| {{Gene|ITGB3}}
| [[CD61]]
| GP3A, GPIIIa
|-
| {{Gene|ITGB4}}
| [[ITGB4|CD104]]
|
|-
| {{Gene|ITGB5}}
| [[Integrin, beta 5|ITGB5]]
| FLJ26658
|-
| {{Gene|ITGB6}}
| [[Integrin, beta 6|ITGB6]]
|
|-
| {{Gene|ITGB7}}
| [[ITGB7]]
|
|-
| {{Gene|ITGB8}}
| [[ITGB8]]
|
|}
{{Multicol-end}}

In addition, variants of some of the subunits are formed by differential splicing; for example four variants of the beta-1 subunit exist. Through different combinations of the α and β subunits, some 24 unique integrins are generated, although the number varies according to different studies.<ref name="hynes1">{{cite journal |author=Hynes R |title=Integrins: bidirectional, allosteric signaling machines |journal=Cell |volume=110 |issue=6 |pages=673–87 |year=2002 |pmid=12297042 |doi = 10.1016/S0092-8674(02)00971-6}}</ref>

Integrin subunits span the [[plasma membrane]] and in general have short cytoplasmic domains of about 40–70 [[amino acid]]s. The exception is the beta-4 subunit, which has a cytoplasmic domain of 1088 amino acids, one of the largest known cytoplasmic domains of any membrane protein. Outside the cell [[plasma membrane]], the α and β chains lie close together along a length of about 23&nbsp;[[nanometre|nm]]; the final 5&nbsp;nm [[N-terminus|N-termini]] of each chain forms a [[ligand (biochemistry)|ligand-binding]] region for the [[extracellular matrix]] (ECM).

The [[molecular mass]] of the integrin subunits can vary from 90&nbsp;[[atomic mass unit|kDa]] to 160&nbsp;kDa. Beta subunits have four [[cysteine]]-rich repeated sequences. Both α and β subunits bind several [[divalent]] [[cation]]s. The role of divalent cations in the α subunit is unknown, but may stabilize the folds of the protein. The cations in the β subunits are more interesting: they are directly involved in coordinating at least some of the [[ligand (biochemistry)|ligands]] that integrins bind.

There are various ways of categorizing the integrins. For example, a subset of the α chains has an additional structural element (or "domain") inserted toward the [[N-terminal]], the alpha-A domain (so called because it has a similar structure to the A-domains found in the protein [[von Willebrand factor]]; it is also termed the α-I domain). Integrins carrying this domain either bind to [[collagen]]s (e.g. integrins α1 β1, and α2 β1), or act as [[Cell (biology)|cell]]-cell adhesion molecules (integrins of the β2 family). This α-I domain is the binding site for ligands of such integrins. Those integrins that don't carry this inserted domain also have an A-domain in their ligand binding site, but ''this'' A-domain is found on the β subunit.

In both cases, the A-domains carry up to three divalent cation binding sites. One is permanently occupied in physiological [[concentration]]s of divalent cations, and carries either a calcium or magnesium ion, the principal divalent cations in blood at median concentrations of 1.4&nbsp;mM (calcium) and 0.8&nbsp;mM (magnesium). The other two sites become occupied by cations when ligands bind—at least for those ligands involving an acidic amino acid in their interaction sites. An acidic amino acid features in the integrin-interaction site of many ECM proteins, for example as part of the amino acid sequence [[Arginine-Glycine-Aspartic acid]] ("RGD" in the one-letter amino acid code).

===High resolution structure===
Despite many years of effort, discovering the high-resolution structure of integrins proved to be challenging: membrane proteins are classically difficult to purify, and integrins are also large, complex and linked to many sugar trees ("highly [[glycosylation|glycosylated]]"). Low-resolution images of detergent extracts of intact integrin GPIIbIIIa, obtained using electron microscopy, and even data from indirect techniques that investigate the solution properties of integrins using ultracentrifugation and light scattering, were combined with fragmentary high-resolution crystallographic or NMR data from single or paired domains of single integrin chains, and molecular models postulated for the rest of the chains.

Despite these wide-ranging efforts, the [[X-ray]] crystal structure obtained for the complete extracellular region of one integrin, αvβ3, was a surprise.<ref>{{cite journal |author=Xiong JP |title=Crystal structure of the extracellular segment of integrin αvβ3 |journal=Science |volume=294 |issue=5541 |pages=339–345 |year=2001 |pmid=11546839 |pmc=2885948 |doi = 10.1126/science.1064535 |last2=Stehle |first2=T |last3=Diefenbach |first3=B |last4=Zhang |first4=R |last5=Dunker |first5=R |last6=Scott |first6=DL |last7=Joachimiak |first7=A |last8=Goodman |first8=SL |last9=Arnaout |first9=MA}}</ref> It showed the molecule to be folded into an inverted V-shape that potentially brings the ligand-binding sites close to the cell membrane. Perhaps more importantly, the crystal structure was also obtained for the same integrin bound to a small ligand containing the RGD-sequence, the drug [[cilengitide]].<ref>{{cite journal |author=Smith J |title=Cilengitide Merck |journal=Curr Opin Investig Drugs |volume=4 |issue=6 |pages=741–5 |year=2003 |pmid=12901235}}</ref> As detailed above, this finally revealed why divalent cations (in the A-domains) are critical for RGD-ligand binding to integrins. The interaction of such sequences with integrins is believed to be a primary switch by which ECM exerts its effects on cell behaviour.

The structure poses many questions, especially regarding ligand binding and signal transduction. The ligand binding site is directed towards the C-terminal of the integrin, the region where the molecule emerges from the cell membrane. If it emerges [[orthogonality|orthogonally]] from the membrane, the ligand binding site would apparently be obstructed, especially as integrin ligands are typically massive and well cross-linked components of the ECM. In fact, little is known about the angle that membrane proteins subtend to the plane of the membrane; this is a problem difficult to address with available technologies. The default assumption is that they emerge rather like little lollipops, but the evidence for this sweet supposition is noticeable by its absence. The integrin structure has drawn attention to this problem, which may have general implications for how membrane proteins work. It appears that the integrin transmembrane helices are tilted (see "Activation" below) which hints that the extracellular chains may also not be orthogonal with respect to the membrane surface.

Although the crystal structure changed surprisingly little after binding to cilengitide, the current hypothesis is that integrin function involves changes in shape to move the ligand-binding site into a more accessible position, away from the cell surface, and this shape change also triggers intracellular signaling. There is a wide body of cell-biological and biochemical literature that supports this view. Perhaps the most convincing evidence involves the use of [[antibody|antibodies]] that only recognize integrins when they have bound to their ligands, or are activated. As the "footprint" that an antibody makes on its binding target is roughly a circle about 3&nbsp;nm in diameter, the resolution of this technique is low. Nevertheless, these so-called LIBS (Ligand-Induced-Binding-Sites) antibodies unequivocally show that dramatic changes in integrin shape routinely occur. However, how the changes detected with antibodies look on the structure is still unknown.

=== Activation ===

When released into the cell membrane, newly synthesized integrin dimers are speculated to be found in the same "bent" conformation revealed by the structural studies described above.  One school of thought claims that this bent form prevents them from interacting with their ligands, although bent forms can predominate in high-resolution EM structures of integrin bound to an ECM ligands. Therefore, at least in biochemical experiments, integrin dimers must apparently not be 'unbent' in order to prime them and allow their binding to the [[Extracellular matrix|ECM]]. In cells, the priming  is accomplished by a protein talin, which binds to the β tail of the integrin dimer and changes its conformation.<ref name="pmid15157154">{{cite journal | author = Calderwood DA | title = Talin controls integrin activation | journal = Biochem. Soc. Trans. | volume = 32 | issue = Pt3 | pages = 434–7 |date=June 2004 | pmid = 15157154 | doi = 10.1042/BST0320434 | url =  }}</ref><ref name="pmid10497155">{{cite journal | author = Calderwood DA, Zent R, Grant R, Rees DJ, Hynes RO, Ginsberg MH | title = The Talin head domain binds to integrin beta subunit cytoplasmic tails and regulates integrin activation | journal = J. Biol. Chem. | volume = 274 | issue = 40 | pages = 28071–4 |date=October 1999 | pmid = 10497155 | doi = 10.1074/jbc.274.40.28071| url =  }}</ref> The α and β integrin chains are both class-I transmembrane proteins: they pass the plasma membrane as single transmembrane alpha-helices. Unfortunately, the helices are too long, and recent studies suggest that, for integrin gpIIbIIIa, they are tilted with respect both to one another and to the plane of the membrane. Talin binding alters the angle of tilt of the β3 chain transmembrane helix in model systems and this may reflect a stage in the process of inside-out signalling which primes integrins.<ref name="PMID20308986">{{cite journal | author = Shattil SJ, Kim C, Ginsberg MH| title = The final steps of integrin activation: the end game | journal =Nature Reviews Molecular Cell Biology  | volume = 11 | pages = 288–300| year = 2010 | pmid = 20308986 | doi = 10.1038/nrm2871 | url =  | issue = 4 }}</ref> Moreover, talin proteins are able to dimerize<ref name="pmid8031639">{{cite journal | author = Goldmann WH, Bremer A, Häner M, Aebi U, Isenberg G | title = Native talin is a dumbbell-shaped homodimer when it interacts with actin | journal = J. Struct. Biol. | volume = 112 | issue = 1 | pages = 3–10 | year = 1994 | pmid = 8031639 | doi = 10.1006/jsbi.1994.1002 | url =  }}</ref> and thus are thought to intervene in the clustering of integrin dimers which leads to the formation of a [[focal adhesion]]. Recently, the [[Kindlin-1]] and [[Kindlin-2]] proteins have also been found to interact with integrin and activate it.<ref name="pmid19240021">{{cite journal | author = Harburger DS, Bouaouina M, Calderwood DA | title = Kindlin-1 and −2 directly bind the C-terminal region of beta integrin cytoplasmic tails and exert integrin-specific activation effects | journal = J. Biol. Chem. | volume = 284 | issue = 17 | pages = 11485–97 |date=April 2009 | pmid = 19240021 | pmc = 2670154 | doi = 10.1074/jbc.M809233200 | url =  }}</ref>

==Function==

Integrins have two main functions:
* Attachment of the cell to the ECM
* Signal transduction from the ECM to the cell

However, they are also involved in a wide range of other biological activities, including immune patrolling, cell migration, and binding to cells by certain viruses, such as [[adenovirus]], [[echovirus]], [[hantavirus]], and [[foot and mouth disease]] viruses.

A prominent function of the integrins is seen in the molecule [[Glycoprotein IIb/IIIa|GPIIbIIIa]], an integrin on the surface of blood [[platelet]]s (thrombocytes) responsible for attachment to fibrin within a developing blood clot. This molecule dramatically increases its binding affinity for fibrin/fibrinogen through association of platelets with  exposed collagens in the wound site. Upon association of platelets with collagen, GPIIbIIIa changes shape, allowing it to bind to fibrin and other blood components to form the clot matrix and stop blood loss.

===Attachment of cell to the ECM===
Integrins couple the ECM outside a cell to the [[cytoskeleton]] (in particular the [[microfilaments]]) inside the cell. Which ligand in the ECM the integrin can bind to is defined by which α and β subunits the integrin is made of. Among the [[ligand]]s of integrins are [[fibronectin]], [[vitronectin]], [[collagen]], and [[laminin]]. The connection between the cell and the ECM may help the cell to endure pulling forces without being ripped out of the ECM. The ability of a cell to create this kind of bond is also of vital importance in [[ontogeny]].

Cell attachment to the ECM is a basic requirement to build a multicellular organism. Integrins are not simply hooks, but give the cell critical signals about the nature of its surroundings. Together with signals arising from receptors for soluble growth factors like [[Vascular endothelial growth factor|VEGF]], [[epidermal growth factor|EGF]], and many others, they enforce a cellular decision on what biological action to take, be it attachment, movement, death, or differentiation. Thus integrins lie at the heart of many cellular biological processes. The attachment of the cell takes place through formation of [[cell adhesion]] complexes, which consist of integrins and many cytoplasmic proteins such as [[talin (protein)|talin]], [[vinculin]], [[paxillin]], and alpha-[[actinin]]. These act by regulating [[kinase]]s such as FAK ([[focal adhesion kinase]]) and [[Src kinase]] family members to phosphorylate substrates such as p130CAS thereby recruiting signaling adaptors such as [[CRK (gene)|CRK]]. These adhesion complexes attach to the actin cytoskeleton. The integrins thus serve to link two networks across the plasma membrane: the extracellular ECM and the intracellular actin filamentous system. Integrin alpha6beta4 is an exception: it links to the keratin intermediate filament system in epithelial cells.

Focal adhesions are large molecular complexes, which are generated following interaction of integrins with ECM, then their clustering.  The clusters likely provide sufficient intracellular binding sites to permit the formation of stable signaling complexes on the cytoplasmic side of the cell membrane. So the focal adhesions contain integrin ligand, integrin molecule, and associate plaque proteins. Binding is propelled by changes in free energy.<ref name="pmid20805876">{{cite journal | author = Olberding JE, Thouless MD, Arruda EM, Garikipati K | editor1-last = Buehler | editor1-first = Markus J. | title = The non-equilibrium thermodynamics and kinetics of focal adhesion dynamics | journal = PLoS ONE | volume = 5 | issue = 8 | pages = e12043 | year = 2010 | pmid = 20805876 | pmc = 2923603 | doi = 10.1371/journal.pone.0012043 | url =  }}</ref> As previously stated, these complexes  connect the extracellular matrix to actin bundles. Cryo-electron tomography reveals that the adhesion contains particles on the cell membrane with diameter of 25 +/- 5&nbsp;nm and spaced at approximately 45&nbsp;nm.<ref name="pmid20694000">{{cite journal | author = Patla I, Volberg T, Elad N, Hirschfeld-Warneken V, Grashoff C, Fässler R, Spatz JP, Geiger B, Medalia O | title = Dissecting the molecular architecture of integrin adhesion sites by cryo-electron tomography | journal = Nat. Cell Biol. | volume = 12 | issue = 9 | pages = 909–15 |date=September 2010 | pmid = 20694000 | doi = 10.1038/ncb2095 | url =  }}</ref> Treatment with Rho-kinase inhibitor [[Y-27632]] reduces the size of the particle, and it is extremely mechanosensitive.<ref name="urlMechanosensitive channels">{{cite web | url = http://www.ks.uiuc.edu/Research/MscLchannel/ | title = Mechanosensitive channels | author = Gullingsrud J, Sotomayor M | authorlink = | coauthors = | date = | format = | work = | publisher = Theoretical and Computational Biophysics Group, Beckman Institute for Advanced Science and Technology: University of Illinois at Urbana-Champaign| pages = | language = | archiveurl = | archivedate = | quote = | accessdate = }}</ref>

One important function of integrins on cells in tissue culture is their role in [[cell migration]]. Cells adhere to a [[substrate (biology)|substrate]] through their integrins. During movement, the cell makes new attachments to the substrate at its front and concurrently releases those at its rear. When released from the substrate, integrin molecules are taken back into the cell by [[endocytosis]]; they are transported through the cell to its front by the [[endocytic cycle]] where they are added back to the surface. In this way they are cycled for reuse, enabling the cell to make fresh attachments at its leading front. It is not yet clear whether cell migration in tissue culture is an artefact of integrin processing, or whether such integrin dependent cell migration also occurs in living organisms.

===Signal transduction===

Integrins play an important role in cell signaling by modulating the cell signaling pathways of transmembrane protein kinases such as receptor tyrosine kinases (RTK). While the interaction between integrin and receptor tyrosine kinases originally  was thought of as uni-directional and supportive, recent studies Indicate that integrins have additional, multi-faceted roles in cell signaling. 
Integrins can regulate the receptor tyrosine kinase signaling by recruiting specific adaptors to the plasma membrane. For example, β1c integrin recruits Gab1/Shp2 and presents Shp2 to IGF1R, resulting in dephosphorylation of the receptor.<ref>{{cite journal|last=Goel|first=H. L.|title=1A Integrin Expression Is Required for Type 1 Insulin-Like Growth Factor Receptor Mitogenic and Transforming Activities and Localization to Focal Contacts|journal=Cancer Research|date=1 August 2005|volume=65|issue=15|pages=6692–6700|doi=10.1158/0008-5472.CAN-04-4315}}</ref>  In a reverse direction, when a receptor tyrosine kinase is activated, integrins co-localise at focal adhesion with the receptor tyrosine kinases and their associated signaling molecules. 

The repertoire of integrins expressed on a particular cell can specify the signaling pathway due to the differential binding affinity of ECM ligands for the integrins. The tissue stiffness and matrix composition can initiate specific signaling pathways regulating cell behavior. Clustering and activation of the integrins/actin complexes strengthen the focal adhesion interaction and initiate the framework for cell signaling through assembly of adhesomes.<ref>{{cite journal|last=Kim|first=Soo-Hyun|coauthors=Turnbull, Jeremy; Guimond, Scott|title=Extracellular matrix and cell signaling: the dynamic cooperation of integrin, proteoglycan and growth factor receptor|journal=Journal of Endocrynology|year=2011|issue=209|pages=139–151}}</ref>  

Depending on the integrin's regulatory impact on specific receptor tyrosine kinases, the cell can experience:
* [[cell growth]],
* [[cell division]],
* cell survival,
* [[cellular differentiation]], and
* [[apoptosis|apoptosis (programmed cell death)]].

Knowledge of the relationship between integrins and receptor tyrosine kinase has laid a foundation for new approaches to cancer therapy. Specifically, targeting integrins associated with RTKs is an emerging approach for inhibiting angiogenesis.<ref>{{cite journal|last=Carbonell|first=W. S.|coauthors=DeLay, M.; Jahangiri, A.; Park, C. C.; Aghi, M. K.|title=1 Integrin Targeting Potentiates Antiangiogenic Therapy and Inhibits the Growth of Bevacizumab-Resistant Glioblastoma|journal=Cancer Research|date=3 May 2013|volume=73|issue=10|pages=3145–3154|doi=10.1158/0008-5472.CAN-13-0011}}</ref>

==Vertebrate integrins==

The following are some of the integrins found in vertebrates:
{| class="wikitable"
| '''Name''' || '''Synonyms''' || '''Distribution''' || '''Ligands'''
 |-
 | '''α<sub>1</sub>β<sub>1</sub>'''  ||VLA-1 ||  Many  || [[Collagen]]s, [[laminin]]s<ref name="lodish">{{cite book | author = Krieger M, Scott MP, Matsudaira PT, Lodish HF, Darnell JE, Zipursky L, Kaiser C, Berk A | authorlink = | editor = | others = | title = Molecular cell biology | edition = fifth | language = | publisher = W.H. Freeman and CO | location = New York | year = 2004 | origyear = | pages = | quote = | isbn = 0-7167-4366-3 | oclc = | doi = | url = | accessdate = }}</ref>
 |-
 | '''α<sub>2</sub>β<sub>1</sub>'''  || VLA-2||  Many  || Collagens, laminins<ref name=lodish/>
 |-
 | '''α<sub>3</sub>β<sub>1</sub>'''  || VLA-3||  Many  || Laminin-5 
 |-
 | '''[[VLA-4|α<sub>4</sub>β<sub>1</sub>]]'''  || VLA-4<ref name=lodish/> ||  [[Hematopoietic]] cells  ||  [[Fibronectin]], [[VCAM-1]]<ref name=lodish/>
 |-
 | '''[[alpha-5 beta-1|α<sub>5</sub>β<sub>1</sub>]]''' || VLA-5; fibronectin receptor || widespread ||  fibronectin<ref name=lodish/> and [[proteinase]]s
 |-
 | '''alpha-6 beta-1|α<sub>6</sub>β<sub>1</sub>''' || VLA-6; laminin receptor || widespread || laminins
 |-
 | '''alpha-7 beta-1|α<sub>7</sub>β<sub>1</sub>''' || || muscle, glioma || laminins
 |-
 | '''[[LFA-1|α<sub>L</sub>β<sub>2</sub>]]'''  || LFA-1<ref name=lodish/> ||  [[T-lymphocyte]]s  || [[ICAM-1]], [[ICAM-2]]<ref name=lodish/>
 |-
 | '''[[Integrin alpha M|α<sub>M</sub>β<sub>2</sub>]]'''  || Mac-1, CR3<ref name=lodish/> ||  [[Neutrophil]]s and [[monocyte]]s  ||  [[Blood plasma|Serum]] proteins, ICAM-1<ref name=lodish/>
 |-
 | '''[[Glycoprotein IIb/IIIa|α<sub>IIb</sub>β<sub>3</sub>]]'''  || Fibrinogen receptor; gpIIbIIIa  <ref>http://www.vetpathology.org/cgi/reprint/34/1/61.pdf Vet Path01 34:61-73 (1997)</ref> || [[Platelet]]s<ref name=lodish/>  ||  fibrinogen, fibronectin<ref name=lodish/>
 |-
 | '''alpha-v beta-1|α<sub>V</sub>β<sub>1</sub>'''  ||  || ocular melanoma; neurologial tumors  ||  [[vitronectin]]; fibrinogen
 |-
 | '''[[alpha-v beta-3|α<sub>V</sub>β<sub>3</sub>]]'''  || vitronectin receptor<ref name="pmid10037797">{{cite journal | author = Hermann P, Armant M, Brown E, Rubio M, Ishihara H, Ulrich D, Caspary RG, Lindberg FP, Armitage R, Maliszewski C, Delespesse G, Sarfati M | title = The vitronectin receptor and its associated CD47 molecule mediates proinflammatory cytokine synthesis in human monocytes by interaction with soluble CD23 | journal = J. Cell Biol. | volume = 144 | issue = 4 | pages = 767–75 |date=February 1999 | pmid = 10037797 | pmc = 2132927 | doi = 10.1083/jcb.144.4.767| url = http://www.jcb.org/cgi/pmidlookup?view=long&pmid=10037797 }}</ref> || activated endothelial cells, melanoma, glioblastoma||  [[vitronectin]],<ref name="pmid10037797"/> fibronectin, fibrinogen, [[osteopontin]], [[CYR61|Cyr61]]
 |-
 | '''[[alpha-v beta-5|α<sub>V</sub>β<sub>5</sub>]]'''  ||  || widespread, esp. fibroblasts, epithelial cells  ||  [[vitronectin]] and adenovirus
 |-
 | '''alpha-v beta-6|α<sub>V</sub>β<sub>6</sub>'''  ||  || proliferating epithelia, esp. lung and mammary gland  ||  [[fibronectin]]; TGFβ1+3
 |-
 | '''alpha-v beta-8|α<sub>V</sub>β<sub>8</sub>'''  ||  || neural tissue; peripheral nerve  ||  [[fibronectin]]; TGFβ1+3
 |-
 | '''α<sub>6</sub>β<sub>4</sub>'''  || || [[Epithelial]] cells<ref name=lodish/>  || [[Laminin]]<ref name=lodish/>
|}

Beta-1 integrins interact with many alpha integrin chains. Gene knockouts of integrins in mice are not always lethal, which suggests that during embryonal development, one integrin may substitute its function for another in order to allow survival. Some integrins are on the cell surface in an inactive state, and can be rapidly primed, or put into a state capable of binding their ligands, by cytokines. Integrins can assume several different well-defined shapes or "conformational states". Once primed, the conformational state changes to stimulate ligand binding, which then activates the receptors — also by inducing a shape change — to trigger outside-in signal transduction.

== References ==

{{Reflist|2}}

==External links==
{{commons-inline|Category:Integrins|Integrins}}
* [http://www.mechanobio.info/Home/glossary-of-terms/proteins/integrin MBInfo - Integrins]
* [http://macromoleculeinsights.com/integrin.php The Integrin Protein]
* [http://www.youtube.com/watch?v=8DOTnKHFTTg Talin substrate for calpain] – PMAP [[The Proteolysis Map]] animation.
* {{MeshName|Integrins}}

{{Integrins}}
{{Cell adhesion molecules}}

[[Category:Integrins]]
[[Category:Transmembrane proteins]]
[[Category:Cell adhesion proteins]]