Integrin beta 2

2019-01-16T03:10:13Z

2601:586:4200:D15E:D4E2:13F:BAC1:EC57: /* Clinical significance */

{{Infobox gene}}
In molecular biology, CD18 ('''Integrin beta chain-2''') is an [[integrin]] beta chain [[protein]] that is encoded by the ''[[ITGB2]]'' [[gene]] in humans.<ref name= AAM1990>{{cite journal|last1=Amin Aanout|first1=M.|title=Structure and Function of the Leukocyte Adhesion Molecules CD11/CD18|journal=Blood|date=March 1, 1990|volume=75|issue=5|pages=1037–1050}}</ref> Upon binding with one of a number of alpha chains, CD18 is capable of forming multiple [[heterodimers]], which play significant roles in cellular adhesion and cell surface signaling, as well as important roles in immune responses.<ref name= AAM1990 /><ref>{{cite web|title=ITGB2 integrin subunit beta 2 [ Homo sapiens (human) ]|url=https://www.ncbi.nlm.nih.gov/gene/3689}}</ref> CD18 also exists in soluble, ligand binding forms. Deficiencies in CD18 expression can lead to adhesion defects in circulating white blood cells in humans, reducing the immune system's ability to fight off foreign invaders.

== Structure and function ==
The ITGB2 protein product is CD18. Integrins are integral cell-surface proteins composed of an alpha chain and a beta chain, and are crucial for cells to be able to efficiently bind to the [[extracellular matrix]].<ref name= AAM1990 /> This is especially important for neutrophils, as cellular adhesion plays a large role in extravasation from the blood vessels. A given chain may combine with multiple partners resulting in different integrins.

The known binding partners of CD18 are [[CD11a]],<ref name= LFA-1>{{cite journal | vauthors = Verma NK, Kelleher D | title = Not Just an Adhesion Molecule: LFA-1 Contact Tunes the T Lymphocyte Program | journal = Journal of Immunology | volume = 199 | issue = 4 | pages = 1213–1221 | date = August 2017 | pmid = 28784685 | doi = 10.4049/jimmunol.1700495 }}</ref> [[CD11b]],<ref name= Mac-1>{{cite journal|last1=Todd|first1=R|title=The continuing saga of complement receptor type 3 (CR3)|journal=Journal of Clinical Investigation|date=1996|volume=98|issue=1|pages=1–2}}</ref> [[CD11c]] and CD11d.<ref name= AAM1990 /> Binding of CD18 and CD11 results in the formation of Lymphocyte Functions Associated Antigen 1 ([[LFA-1]]),<ref name= LFA-1 /> a protein found on [[B cells]], all [[T cells]], [[macrophages]], [[neutrophils]] and [[NK cells]]. LFA-1 is involved in adhesion and binding to [[antigen presenting cells]] through interactions with the surface protein [[ICAM-1]]

Binding of CD18 and CD11b-d results in the formation of [[complement receptors]] (e.g. [[Macrophage-1 antigen]] receptor, Mac-1, when bound to CD11b),<ref name= Mac-1 /> which are proteins found largely on neutrophils, macrophages and NK cells. These complement receptors participate in the [[innate immune response]] by recognizing foreign antigen peptides and [[Phagocytosis|phagocytizing]] them, thus destroying the antigen.

== Clinical significance ==
In humans, lack of functional CD18 causes [[Leukocyte Adhesion Deficiency]], a disease defined by a lack of leukocyte [[extravasation]] from blood into tissues, which is the inability of circulating leukocytes to respond to foreign bodies present in the tissue.<ref>{{cite journal | vauthors = Kishimoto TK, Hollander N, Roberts TM, Anderson DC, Springer TA | title = Heterogeneous mutations in the beta subunit common to the LFA-1, Mac-1, and p150,95 glycoproteins cause leukocyte adhesion deficiency | journal = Cell | volume = 50 | issue = 2 | pages = 193–202 | date = July 1987 | pmid = 3594570 }}</ref> This subsequently reduces the ability of the individual's immune system to fight off infection, making them more susceptible to foreign infection than those with functional CD18 proteins. The beta 2 integrins have also been found in a [[soluble]] form, meaning they are not anchored into the plasma membrane of the cell, but rather exist outside of the cell in the plasma, and are capable of ligand binding.<ref>{{cite journal | vauthors = Gjelstrup LC, Boesen T, Kragstrup TW, Jørgensen A, Klein NJ, Thiel S, Deleuran BW, Vorup-Jensen T | title = Shedding of large functionally active CD11/CD18 Integrin complexes from leukocyte membranes during synovial inflammation distinguishes three types of arthritis through differential epitope exposure | journal = Journal of Immunology | volume = 185 | issue = 7 | pages = 4154–68 | date = October 2010 | pmid = 20826754 | doi = 10.4049/jimmunol.1000952 }}</ref> The soluble beta 2 integrins are ligand binding and plasma levels are inversely associated with disease activity in the autoimmune disease spondyloarthritis.<ref>{{cite journal | vauthors = Kragstrup TW, Jalilian B, Hvid M, Kjærgaard A, Østgård R, Schiøttz-Christensen B, Jurik AG, Robinson WH, Vorup-Jensen T, Deleuran B | title = Decreased plasma levels of soluble CD18 link leukocyte infiltration with disease activity in spondyloarthritis | journal = Arthritis Research & Therapy | volume = 16 | issue = 1 | pages = R42 | date = February 2014 | pmid = 24490631 | doi = 10.1186/ar4471 }}</ref>

== Interactions ==
CD18 has been shown to [[Protein-protein interaction|interact]] with:
{{div col|colwidth=20em}}
* [[FHL2]],<ref name = pmid10906324>{{cite journal | vauthors = Wixler V, Geerts D, Laplantine E, Westhoff D, Smyth N, Aumailley M, Sonnenberg A, Paulsson M | title = The LIM-only protein DRAL/FHL2 binds to the cytoplasmic domain of several alpha and beta integrin chains and is recruited to adhesion complexes | journal = The Journal of Biological Chemistry | volume = 275 | issue = 43 | pages = 33669–78 | date = October 2000 | pmid = 10906324 | doi = 10.1074/jbc.M002519200 }}</ref>
* [[GNB2L1]],<ref name = pmid9442085>{{cite journal | vauthors = Liliental J, Chang DD | title = Rack1, a receptor for activated protein kinase C, interacts with integrin beta subunit | journal = The Journal of Biological Chemistry | volume = 273 | issue = 4 | pages = 2379–83 | date = January 1998 | pmid = 9442085 | doi = 10.1074/jbc.273.4.2379 }}</ref>
* [[ICAM-1]],<ref name = pmid10352278>{{cite journal | vauthors = Kotovuori A, Pessa-Morikawa T, Kotovuori P, Nortamo P, Gahmberg CG | title = ICAM-2 and a peptide from its binding domain are efficient activators of leukocyte adhesion and integrin affinity | journal = Journal of Immunology | volume = 162 | issue = 11 | pages = 6613–20 | date = June 1999 | pmid = 10352278 | doi = }}</ref><ref name = pmid11279101>{{cite journal | vauthors = Lu C, Takagi J, Springer TA | title = Association of the membrane proximal regions of the alpha and beta subunit cytoplasmic domains constrains an integrin in the inactive state | journal = The Journal of Biological Chemistry | volume = 276 | issue = 18 | pages = 14642–8 | date = May 2001 | pmid = 11279101 | doi = 10.1074/jbc.M100600200 }}</ref><ref name = pmid7642561>{{cite journal | vauthors = Huang C, Springer TA | title = A binding interface on the I domain of lymphocyte function-associated antigen-1 (LFA-1) required for specific interaction with intercellular adhesion molecule 1 (ICAM-1) | journal = The Journal of Biological Chemistry | volume = 270 | issue = 32 | pages = 19008–16 | date = August 1995 | pmid = 7642561 | doi = 10.1074/jbc.270.32.19008 }}</ref> and
* [[PSCD1]].<ref name = pmid9765275>{{cite journal | vauthors = Rietzler M, Bittner M, Kolanus W, Schuster A, Holzmann B | title = The human WD repeat protein WAIT-1 specifically interacts with the cytoplasmic tails of beta7-integrins | journal = The Journal of Biological Chemistry | volume = 273 | issue = 42 | pages = 27459–66 | date = October 1998 | pmid = 9765275 | doi = 10.1074/jbc.273.42.27459 }}</ref><ref name = pmid10835351>{{cite journal | vauthors = Geiger C, Nagel W, Boehm T, van Kooyk Y, Figdor CG, Kremmer E, Hogg N, Zeitlmann L, Dierks H, Weber KS, Kolanus W | title = Cytohesin-1 regulates beta-2 integrin-mediated adhesion through both ARF-GEF function and interaction with LFA-1 | journal = The EMBO Journal | volume = 19 | issue = 11 | pages = 2525–36 | date = June 2000 | pmid = 10835351 | pmc = 212768 | doi = 10.1093/emboj/19.11.2525 }}</ref>
{{Div col end}}

== See also ==
* [[leukocyte adhesion deficiency]]
* [[integrin]]

== References ==
{{reflist}}

== Further reading ==
{{refbegin | 2}}
* {{cite journal | vauthors = Bunting M, Harris ES, McIntyre TM, Prescott SM, Zimmerman GA | title = Leukocyte adhesion deficiency syndromes: adhesion and tethering defects involving beta 2 integrins and selectin ligands | journal = Current Opinion in Hematology | volume = 9 | issue = 1 | pages = 30–5 | date = January 2002 | pmid = 11753075 | doi = 10.1097/00062752-200201000-00006 }}
* {{cite journal | vauthors = Roos D, Law SK | title = Hematologically important mutations: leukocyte adhesion deficiency | journal = Blood Cells, Molecules & Diseases | volume = 27 | issue = 6 | pages = 1000–4 | year = 2003 | pmid = 11831866 | doi = 10.1006/bcmd.2001.0473 }}
* {{cite journal | vauthors = Gahmberg CG, Fagerholm S | title = Activation of leukocyte beta2-integrins | journal = Vox Sanguinis | volume = 83 Suppl 1 | issue = | pages = 355–8 | date = August 2002 | pmid = 12617168 | doi = 10.1111/j.1423-0410.2002.tb05333.x }}
* {{cite journal | vauthors = Schymeinsky J, Mócsai A, Walzog B | title = Neutrophil activation via beta2 integrins (CD11/CD18): molecular mechanisms and clinical implications | journal = Thrombosis and Haemostasis | volume = 98 | issue = 2 | pages = 262–73 | date = August 2007 | pmid = 17721605 | doi = 10.1160/th07-02-0156 }}
{{refend}}

== External links ==
* {{MeshName|CD18+antigen}}
*[http://cmkb.cellmigration.org/report.cgi?report=orth_overview&orth_acc=co00001789 ITGB2] Info with links in the [http://www.cellmigration.org/index.shtml Cell Migration Gateway]
* {{UCSC gene info|ITGB2}}

{{PDB Gallery|geneid=3689}}
{{Clusters of differentiation}}
{{Clusters of differentiation by lineage}}
{{Complement system}}
{{Cell adhesion molecules}}
{{Integrins}}

{{Use dmy dates|date=April 2017}}

[[Category:Integrins]]
[[Category:Clusters of differentiation]]

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Integrin beta 2