FEBS Letters
Volume 579, Issue 1 , Pages 25-29, 3 January 2005

Mapping the interaction of bradykinin 1–5 with the exodomain of human protease activated receptor 4

Edited by Veli-Pekka Lehto

  • Marvin T. Nieman

      Affiliations

    • Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109-0640, USA
    • Thromgen, Inc., Ann Arbor, MI 48104, USA
    • ,
  • Eileen Pagan-Ramos

      Affiliations

    • Thromgen, Inc., Ann Arbor, MI 48104, USA
    • ,
  • Mark Warnock

      Affiliations

    • Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109-0640, USA
    • Thromgen, Inc., Ann Arbor, MI 48104, USA
    • ,
  • Yelena Krijanovski

      Affiliations

    • Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109-0640, USA
    • ,
  • Ahmed A.K. Hasan

      Affiliations

    • Thromgen, Inc., Ann Arbor, MI 48104, USA
    • ,
  • Alvin H. Schmaier

      Affiliations

    • Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109-0640, USA
    • Thromgen, Inc., Ann Arbor, MI 48104, USA
    • Corresponding Author InformationCorresponding author. Fax: +1 734 6475669

Received 8 September 2004; received in revised form 1 November 2004; accepted 4 November 2004. published online 30 November 2004.

Abstract 

The angiotensin converting enzyme breakdown product of bradykinin, bradykinin 1–5 (RPPGF), inhibits thrombin-induced human or mouse platelet aggregation. RPPGF binds to the exodomain of human protease-activated receptor 1 (PAR1). Studies determined if RPPGF also binds to the exodomain of human PAR4. RPPGF binds to a peptide of the thrombin cleavage site on PAR4. Recombinant wild-type and mutated exodomain of human PAR4 was prepared. The N-terminal arginine on RPPGF binds to the P2 position or proline46 on PAR4 to block thrombin cleavage. These data indicate that RPPGF influences thrombin activity by binding to the thrombin cleavage site on both PAR4 and PAR1.

Abbreviations: RPPGF or BK1–5, bradykinin 1–5, PAR1 & 4, protease-activated receptors 1 & 4, SIL12, peptide SILPAPRGYPGQ

Keywords: Thrombin, PAR4, Bradykinin, Bradykinin 1–5, RPPGF

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PII: S0014-5793(04)01419-X

doi:10.1016/j.febslet.2004.11.041

FEBS Letters
Volume 579, Issue 1 , Pages 25-29, 3 January 2005

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