Volume 272, Number 2,
Issue of January 10, 1997
pp. 1323-1330
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.
Stimulation of Platelet Activation and Aggregation by a
Carboxyl-terminal Peptide from Thrombospondin Binding to the
Integrin-associated Protein Receptor
(Received for publication, August 31, 1996)
Douglas J.
Dorahy
,
Rick F.
Thorne
,
John V.
Fecondo
§
and
Gordon F.
Burns
From the 
Cancer Research Unit, Faculty of Medicine
and Health Sciences, The University of Newcastle, Callaghan, New
South Wales 2308, Australia and the § School of Chemical
Sciences, Swinburne University of Technology,
Hawthorn, Victoria 3122, Australia
Thrombospondin, a major secretory product of the
-granules of activated platelets, is a large trimeric glycoprotein
that plays an important role in platelet aggregation. On resting
platelets, thrombospondin binds to a single receptor in a
cation-independent manner, but upon platelet activation it binds at
least two further, distinct receptors that are both dependent upon
divalent cations. Each of these receptors on the platelet surface binds
to different regions of the thrombospondin molecule, and such binding
may be responsible for the multifunctional role of thrombospondin in aggregation. We show here that a peptide from the carboxyl terminus of
thrombospondin, RFYVVMWK, directly and specifically induces the
activation and aggregation of washed human platelets from different
donors at concentrations of 5-25 µM. At lower
concentrations the peptide synergizes with suboptimal concentrations of
ADP to induce aggregation. Peptide affinity chromatography and
immunoprecipitation with a monoclonal antibody were used to identify
the receptor for the carboxyl-terminal peptide as the
integrin-associated protein. The integrin-associated protein remained
bound to the RFYVVMWK-containing peptide column when washed with a
scrambled peptide in the presence of 5 mM EDTA, indicating
a divalent cation-independent association. It is suggested that
integrin-associated protein is the primary receptor for thrombospondin
on the surface of resting platelets and is implicated in potentiating
the platelet aggregation response.
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