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(Received for publication, March 28, 1996)
From Recently, a second member of the
protease-activated receptor (PAR) family, named PAR-2, has been
identified. Similar to the thrombin receptor, PAR-2 appears to be
activated by proteolytic-mediated exposure of a ``tethered ligand''
sequence and can also be activated by the corresponding synthetic
peptides. Similarities in the amino acid sequence of the receptors'
tethered ligand sequences suggest that their respective agonist
peptides might not be absolutely specific for their particular
receptors. To test this, the receptor specificity of each agonist has
been determined by measuring the responses of Xenopus
oocytes expressing the thrombin receptor or PAR-2 to agonist peptides
or enzymes. Thrombin receptors responded to thrombin, the human
thrombin receptor-activating peptide SFLLRNP-NH2 (TRAP)
(EC50 = 0.1 µM), and Xenopus
TRAP, TFRIFD-NH2 (EC50 = 1 µM),
but did not show any increase in calcium efflux over control levels
with trypsin (50 nM) or PAR-2 agonist peptides (100 µM). Human and murine PAR-2 receptors responded
comparably to human and murine PAR-2 agonist peptides (SLIGKVD and
SLIGRL, respectively) (EC50 = 0.5-2.0 µM)
and trypsin, but not to thrombin. PAR-2 was also found to be responsive
to TRAP (EC50 = 1 µM) but was unresponsive to
Xenopus TRAP (50 µM). Responses to additional
peptide agonist analogs suggest that an amino-terminal serine is
critical for PAR-2 agonist activity.
Volume 271, Number 28,
Issue of July 12, 1996
pp. 16466-16471
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
,
,
,
,
COR Therapeutics, Inc., South San Francisco,
California 94080 and the ¶ Division of Molecular Neurobiology,
The Wallenberg Laboratory, Lund University,
S-220 07 Lund, Sweden
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