Integrin alpha 2b beta 3, Recombinant, Human (alphaIIbbeta3, GPIIbIIIa, CD41)

Integrin alpha2bbeta3 (also alphaIIbbeta3 or GPIIbIIIa) is the only alpha2b integrin and shares the beta3 subunit only with alphaVbeta3 (1-3). It is the non-covalent heterodimer of type I transmembrane subunits, alpha2b/CD41 (present as a disulfide-linked complex of 114kD heavy and 22kD light chains) and 93kD beta3/CD61 (1-3). It is the most abundant integrin expressed by megakaryocytes and platelets, both on the surface and within alpha granules (1, 2). Deficiencies of alpha2bbeta3 produce Glanzmann thrombasthenia, a potentially serious bleeding disorder (4). In its constitutively inactive state, alpha2bbeta3 is flexed within the extracellular domains. Activation, either by intracellular signaling or by Mg2+ or Mn2+ binding, extends the integrin to expose the ligand binding site created by interaction of the beta3 vWFA domain with the alpha2b beta-propeller structure (1). The 962aa human alpha2b ECD shares 78-83% aa sequence identity with mouse, rat, canine, equine and porcine alpha2b while the 685aa human beta3 ECD shares 95% aa identity with horse and dog, and 89-92% aa identity with mouse, rat and porcine beta3. It is unclear whether splice variants of beta3 that differ in the cytoplasmic domain are expressed significantly in platelets (5-7). However, platelet expression of a beta3 splice variant that produces a soluble 60kD beta3 isoform, and an alpha2b isoform lacking aa948-982, have been reported (7, 8). Active cell surface alpha2bbeta3 adheres to fibrinogen, mediating platelet/platelet interactions that initiate a cascade of platelet activation and aggregation, extracellular matrix adhesion, formation of thrombi and clot retraction (1). It also binds matrix proteins that have an RGD motif, including fibronectin, plasminogen, prothrombin, thrombospondin and vitronectin (1, 2). Targeting of alpha2bbeta3 by therapeutic antibodies or small molecules can inhibit formation of thrombi in patients with acute coronary syndrome, and potentially inhibits tumor angiogenesis and metastasis by blocking interaction of platelet alpha2bbeta3 with tumor cells (1, 9).\n\nSource:\nRecombinant protein corresponding to human Integrin alpha 2b beta 3, CHO-derived.\n\nMolecular Weight: \n~140-150kD & ~110-120kD\n\nEndotoxin:\n<1.0EU/1ug (LAL method).\n\nStorage and Stability:\nLyophilized powder may be stored at -20 degrees C. Stable for 12 months at -20 degrees C. Reconstitute with sterile PBS. Aliquot to avoid repeated freezing and thawing. Store at -20 degrees C. Reconstituted product is stable for 6 months at -20 degrees C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer.

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SPECIFICATIONS

Catalog Number

145809

Size

25ug

Form

Supplied as a lyophilized powder in PBS. Reconstitute in 200ug/ml PBS.

Purity

~95% (SDS-PAGE)

References

1. Kasirer-Friede, A. et al. (2007) Immunol. Rev. 218:247. 2. Poncz, M. et al. (1987) J. Biol. Chem. 262:8476. 3. Fitzgerald, L.A. et al. (1987) J. Biol. Chem. 262:3936. 4. Franchini, M. et al. (2010) Clin. Chim. Acta 411:1. 5. Kumar, C. S. et al. (1987) J. Biol. Chem. 272:16390. 6. van Kuppevelt, H. et al. (1989) Proc. Natl. Acad. Sci. USA 86:5415. 7. Djaffar, I. et al. (1994) Biochem. J. 300:67. 8. Bray, P.F. et al. (1990) J. Biol. Chem. 265:9587. 9. Erpenbeck, L. and M.P. Schon (2010) Blood 115:3427.