Glycoprotein IIb/IIIa
| integrin, alpha 2b (platelet glycoprotein IIb of IIb/IIIa complex, antigen CD41) | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Symbol | ITGA2B | ||||||
| Alt. symbols | GP2B | ||||||
| NCBI gene | 3674 | ||||||
| HGNC | 6138 | ||||||
| OMIM | 607759 | ||||||
| RefSeq | NM_000419 | ||||||
| UniProt | P08514 | ||||||
| Other data | |||||||
| Locus | Chr. 17 q21.32 | ||||||
| |||||||
| integrin, beta 3 (platelet glycoprotein IIIa, antigen CD61) | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Symbol | ITGB3 | ||||||
| Alt. symbols | GP3A | ||||||
| NCBI gene | 3690 | ||||||
| HGNC | 6156 | ||||||
| OMIM | 173470 | ||||||
| RefSeq | NM_000212 | ||||||
| UniProt | P05106 | ||||||
| Other data | |||||||
| Locus | Chr. 17 q21.32 | ||||||
| |||||||
In biochemistry and medicine, glycoprotein IIb/IIIa (GPIIb/IIIa, also known as integrin αIIbβ3) is an integrin complex found on platelets. It is a transmembrane receptor for fibrinogen[1] and von Willebrand factor, and aids platelet activation. The complex is formed via calcium-dependent association of gpIIb and gpIIIa, a required step in normal platelet aggregation and endothelial adherence.[2][3] Platelet activation by ADP (blocked by clopidogrel) leads to the aforementioned conformational change in platelet gpIIb/IIIa receptors that induces binding to fibrinogen.[1] The gpIIb/IIIa receptor is a target of several drugs including abciximab, eptifibatide, and tirofiban.
gpIIb/IIIa complex formation
[edit]Once platelets are activated, granules secrete clotting mediators, including both ADP and TXA2. These then bind their respective receptors on platelet surfaces, in both an autocrine and paracrine fashion (binds both itself and other platelets). The binding of these receptors result in a cascade of events resulting in an increase in intracellular calcium (e.g. via Gq receptor activation leading to Ca2+ release from platelet endoplasmic reticulum Ca2+ stores, which may activate Protein Kinase C). Hence, this calcium increase triggers the calcium-dependent association of gpIIb and gpIIIa to form the activated membrane receptor complex gpIIb/IIIa, which is capable of binding fibrinogen (factor I), resulting in many platelets "sticking together" as they may connect to the same strands of fibrinogen, resulting in a clot. The coagulation cascade then follows to stabilize the clot, as thrombin (factor IIa) converts the soluble fibrinogen into insoluble fibrin strands. These strands are then cross-linked by factor XIII to form a stabilized blood clot.
Pathology
[edit]Defects in glycoprotein IIb/IIIa cause Glanzmann's thrombasthenia.[4]
Autoantibodies against IIb/IIIa can be produced in immune thrombocytopenic purpura.[5]
Medicine
[edit]Glycoprotein IIb/IIIa inhibitors like abciximab can be used to prevent blood clots in an effort to decrease the risk of heart attack or stroke.
See also
[edit]References
[edit]- ^ a b Vickers JD (July 1999). "Binding of polymerizing fibrin to integrin alpha(IIb)beta(3) on chymotrypsin-treated rabbit platelets decreases phosphatidylinositol 4,5-bisphosphate and increases cytoskeletal actin". Platelets. 10 (4): 228–37. doi:10.1080/09537109976077. PMID 16801097.
- ^ Calvete JJ (April 1995). "On the structure and function of platelet integrin alpha IIb beta 3, the fibrinogen receptor". Proceedings of the Society for Experimental Biology and Medicine. 208 (4): 346–60. doi:10.3181/00379727-208-43863a. PMID 7535429. S2CID 9298838.
- ^ Shattil SJ (August 1999). "Signaling through platelet integrin alpha IIb beta 3: inside-out, outside-in, and sideways". Thrombosis and Haemostasis. 82 (2): 318–25. doi:10.1055/s-0037-1615849. PMID 10605720. S2CID 83902334.
- ^ Bellucci S, Caen J (September 2002). "Molecular basis of Glanzmann's Thrombasthenia and current strategies in treatment". Blood Reviews. 16 (3): 193–202. doi:10.1016/S0268-960X(02)00030-9. PMID 12163005.
- ^ McMillan R (October 2007). "The pathogenesis of chronic immune thrombocytopenic purpura". Seminars in Hematology. 44 (4 Suppl 5): S3–S11. doi:10.1053/j.seminhematol.2007.11.002. PMID 18096470.
External links
[edit]- Glycoproteins+IIb-IIIa at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
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