Distinct Domains of αIIbβ3 Support Different Aspects of Outside-In Signal Transduction and Platelet Activation Induced by LSARLAF, an αIIbβ3 Interacting Peptide

Jerry M. Derrick; Sanford J. Shattil; Mortimer Poncz; Ralph A. Gruppo; Kent T. Gartner

doi:10.1055/s-0037-1616147

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2001; 86(03): 894-901
DOI: 10.1055/s-0037-1616147

Review Articles

Schattauer GmbH

Distinct Domains of αIIbβ3 Support Different Aspects of Outside-In Signal Transduction and Platelet Activation Induced by LSARLAF, an αIIbβ3 Interacting Peptide

Authors

Jerry M. Derrick

¹University of Memphis, Department of Microbiology and Molecular Cell Biology, Memphis, TN
Sanford J. Shattil

²Scripps Research Institute, Department of Vascular Biology, LaJolla, CA
Mortimer Poncz

³University of Pennsylvania School of Medicine, Departments of Pediatrics and Medicine, Philadelphia, PA
Ralph A. Gruppo

⁴Children’s Hospital Medical Center, Division of Hematology/Oncology, Cincinnati, OH, USA
Kent T. Gartner

¹University of Memphis, Department of Microbiology and Molecular Cell Biology, Memphis, TN

Abstract

Summary

The peptide LSARLAF causes αIIbβ3-dependent platelet activation exemplified by secretion, aggregation, spreading and adhesion on fibrinogen, and tyrosine phosphorylation. αIIbβ3-dependent outside-in signal transduction induced by LSARLAF was investigated in variant thrombasthenic platelets which lack most of the cytoplasmic domain of the integrin β3 subunit (αIIbβ3 Δ724). These studies revealed that only certain aspects of this αIIbβ3-dependent outside-in signaling were affected by the β3 truncation. Specifically, αIIbβ3 724 supported LSARLAF-induced platelet aggregation, agglutination and secretion, but failed to trigger cytoskeletal reorganization and platelet spreading on fibrinogen, despite the fact that PMA-induced non αIIbβ3 mediated signaling caused spreading of these platelets on fibrinogen. Thus, distinct domains of αIIbβ3 are required to support different aspects of LSARLAF-induced platelet activation. Furthermore, these studies suggest that not all αIIbβ3-dependent platelet responses require an intact β3 cytoplasmic tail.

Keywords

Outside-in signaling - platelet spreading - tyrosine phosphorylation

Full Text

References

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