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Enzymatic activation of PAR-2
S
L
a Cleavage by
trypsin
tryptase
FVIIa
FXa
Non-enzymatic activation of PAR-2
RG K
NH2
I
S
L
NH2
I
PAR-2
G
R
L
RG K
G
R
L
Cell
COOH
COOH
NH2
K
G
R
H2N
S L I GR L
COOH
COOH
e Addition of
synthetic peptide
b Release of peptide
S
L
I
G
RRG
I
LL
L
c Formation of
tethered ligand
SR
GK
NH2
L
I
G H2N
R
S L I G R L COOH
L
S
COOH
COOH
d
f
Peptide binding
to PAR-2 mimics
tethered ligand
g
Activation
Enzymatic and non-enzymatic activation mechanisms of PAR-2
(protease-activated receptor 2)
Expert Reviews in Molecular Medicine C 2002 Cambridge University Press
Figure 1. Enzymatic and non-enzymatic activation mechanisms of PAR-2 (protease-activated
receptor 2). (a) Endogenous proteases such as trypsin, tryptase and coagulation factors VIIa (FVIIa) and Xa
(FXa) enzymatically cleave the N-terminal peptide of PAR-2 (protease-activated receptor 2), a seventransmembrane-type receptor, at a specific site, (b) releasing a peptide. (c) The new N-terminal end of PAR-2
(NH2-SLIGRL- for murine PAR-2) then binds to the second loop of the PAR-2 molecule, and therefore constitutes
an exposed tethered ligand. (d) This activates the receptor, triggering an intracellular G-protein-coupled pathway
that results in Ca2+ mobilisation and activation of protein kinase C (downstream pathway not shown). (e) A
synthetic SLIGRL peptide, based on the amino acid sequence of the tethered ligand, (f) directly binds to the
body of PAR-2 without cleaving the N-terminal peptide, thereby (g) mimicking the effect of the PAR-2-activating
proteases (fig001akk).
Accession information: (02)00480-5a.pdf (short code: fig001akk); 16 July 2002
ISSN 1462-3994 ©2002 Cambridge University Press
Enzymatic and non-enzymatic activation mechanisms of PAR-2
(protease-activated receptor 2)
in molecular medicine
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