Glycoprotein IIb/IIIa

integrin, beta 3 (platelet glycoprotein IIIa, antigen CD61)
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
Structures
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Structures	Swiss-model
Domains	InterPro

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Structures	Swiss-model
Domains	InterPro

integrin, alpha 2b (platelet glycoprotein IIb of IIb/IIIa complex, antigen CD41)
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
Structures
Search for
Structures	Swiss-model
Domains	InterPro

In biochemistry and medicine, glycoprotein IIb/IIIa (GPIIb/IIIa, also known as integrin α_IIbβ₃) 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

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 G_q 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

Defects in glycoprotein IIb/IIIa cause Glanzmann's thrombasthenia.^[4]

Autoantibodies against IIb/IIIa can be produced in immune thrombocytopenic purpura.^[5]

Medicine

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.

References

^ ^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

Glycoproteins IIb-IIIa at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This article on a gene on human chromosome 17 is a stub. You can help Wikipedia by expanding it.

[Vickers_1999-1] 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.

[pmid7535429-2] 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.

[pmid10605720-3] 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.

[pmid12163005-4] 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.

[pmid18096470-5] 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.

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