Glycoprotein IIb/IIIa

{{protein

| Name = integrin, alpha 2b (platelet glycoprotein IIb of IIb/IIIa complex, antigen CD41)

| caption =

| image =

| width =

| HGNCid = 6138

| Symbol = ITGA2B

| AltSymbols = GP2B

| EntrezGene = 3674

| OMIM = 607759

| RefSeq = NM_000419

| UniProt = P08514

| PDB =

| ECnumber =

| Chromosome = 17

| Arm = q

| Band = 21.32

| LocusSupplementaryData =

}}

{{protein

| Name = integrin, beta 3 (platelet glycoprotein IIIa, antigen CD61)

| caption =

| image =

| width =

| HGNCid = 6156

| Symbol = ITGB3

| AltSymbols = GP3A

| EntrezGene = 3690

| OMIM = 173470

| RefSeq = NM_000212

| UniProt = P05106

| PDB =

| ECnumber =

| Chromosome = 17

| Arm = q

| Band = 21.32

| LocusSupplementaryData =

}}

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 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.{{cite journal | vauthors = Calvete JJ | title = On the structure and function of platelet integrin alpha IIb beta 3, the fibrinogen receptor | journal = Proceedings of the Society for Experimental Biology and Medicine | volume = 208 | issue = 4 | pages = 346–60 | date = April 1995 | pmid = 7535429 | doi = 10.3181/00379727-208-43863a | s2cid = 9298838 }}{{cite journal | vauthors = Shattil SJ | title = Signaling through platelet integrin alpha IIb beta 3: inside-out, outside-in, and sideways | journal = Thrombosis and Haemostasis | volume = 82 | issue = 2 | pages = 318–25 | date = August 1999 | pmid = 10605720 | doi = 10.1055/s-0037-1615849| s2cid = 83902334 }} Platelet activation by ADP (blocked by clopidogrel) leads to the aforementioned conformational change in platelet gpIIb/IIIa receptors that induces binding to fibrinogen.{{cite journal | vauthors = Vickers JD | title = Binding of polymerizing fibrin to integrin alpha(IIb)beta(3) on chymotrypsin-treated rabbit platelets decreases phosphatidylinositol 4,5-bisphosphate and increases cytoskeletal actin | journal = Platelets | volume = 10 | issue = 4 | pages = 228–37 | date = July 1999 | pmid = 16801097 | doi = 10.1080/09537109976077 }} 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.{{cite journal | vauthors = Bellucci S, Caen J | title = Molecular basis of Glanzmann's Thrombasthenia and current strategies in treatment | journal = Blood Reviews | volume = 16 | issue = 3 | pages = 193–202 | date = September 2002 | pmid = 12163005 | doi = 10.1016/S0268-960X(02)00030-9 }}

Autoantibodies against IIb/IIIa can be produced in immune thrombocytopenic purpura.{{cite journal | vauthors = McMillan R | title = The pathogenesis of chronic immune thrombocytopenic purpura | journal = Seminars in Hematology | volume = 44 | issue = 4 Suppl 5 | pages = S3–S11 | date = October 2007 | pmid = 18096470 | doi = 10.1053/j.seminhematol.2007.11.002 }}

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

External links

{{MeshName|Glycoproteins+IIb-IIIa}}

Category:Integrins