Thrombspondin Acts via Integrin-associated Protein to Activate the Platelet Integrin αIIbβ3 *

Integrin-associated protein (IAP or CD47) is a receptor for the cell/platelet-binding domain (CBD) of thrombospondin-1 (TS1), the most abundant protein of platelet α granules. Although it associates with αIIbβ3, IAP has no known function in platelets. TS1, the CBD, and an IAP agonist peptide (4N1K) from the CBD of TS1 activate the platelet integrin αIIbβ3, resulting in platelet spreading on immobilized fibrinogen, stimulation of platelet aggregation, and enhanced tyrosine phosphorylation of focal adhesion kinase. Furthermore, 4N1K peptide selectively stimulates the phosphorylation of LYN and SYK and their association with FAK. The phosphorylation of SYK is blocked by pertussis toxin, implicating a Gi-like heterotrimeric G protein. IAP solublized from membranes of unstimulated platelets binds specifically to an affinity column of 4N1K peptide. Both αIIb and β3 integrin subunits and c-Src bind along with IAP. This complex of proteins is also detected with immunoprecipitation. Activation of platelets with the agonist peptide 4N1K results in the association of FAK with the IAP-αIIbβ3 complex. Thus an important function of TS1 in platelets is that of a secreted costimulator of αIIbβ3 whose unique properties result in its localization to the platelet surface and the fibrin clot.

• Publication year

  1997

• Venue

  Journal of Biological Chemistry

• Publication date

  1997-06-06

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/JBC.272.23.14740PMID 9169439
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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