Protease-Activated Receptor Genes Are Clustered on 5q13
Véronique Guyonnet Dupérat,
Béatrice Jacquelin,
Pierre Boisseau,
Benoît Arveiler, and
Alan T. Nurden
From UMR 5533 CNRS, Hôpital Cardiologique, Pessac, France; and
Laboratoire de Pathologie Moléculaire et Thérapie
Génique, Université Victor Segalen Bordeaux 2, France.
The serine protease, thrombin, is both a potent agonist for platelet
aggregation and a mitogen inducing the proliferation of other cell
types. Many cellular responses to thrombin are mediated by a
G-protein-coupled thrombin receptor (protease-activated receptor-1, PAR-1). This represents the prototype of a new family of
proteolytically cleaved receptors that includes PAR-2 and the recently
identified PAR-3. Like PAR-1, PAR-3 is a potential thrombin receptor.
Their similar gene structure, mechanism of activation, and
colocalization to 5q13 raises the question of a common evolutionary
origin and of their belonging to a clustered gene family. Construction
of a physical map of the 5q13 region by pulsed-field gel
electrophoresis (PFGE) has allowed us to identify six potential CpG
islands and to establish a linkage of the PAR genes. Southern blot
analysis showed that they were in a cluster on a 560-kb Asc I
fragment, in the order PAR-2, PAR-1, and PAR-3. PAR-1 and PAR-2 genes
were contained within the identical 240-kb Not I fragment, thus
confirming a tight linkage between them. The localization of other CpG
islands suggested that more PAR-family genes may be present.
Blood, Vol. 92 No. 1 (July 1), 1998:
pp. 25-31
© 1998 by The American Society of Hematology.
