THE HUMAN THROMBIN RECEPTOR AND PROTEINASE ACTIVATED RECEPTOR-2 GENESARE TIGHTLY LINKED ON CHROMOSOME 5Q13

The thrombin receptor (TR) and proteinase activated receptor-2 (PAR-2) map represent the prototypes of an emerging family of cell-surface re ceptors that effect cell activation events mediated by serine protease s generated during inflammatory, fibrinolytic or haemostatic-regulated pathways. To further characterize the molecular genetics of these rec eptors, we have refined the genetic and physical mapping of both PAR-2 and TR. Utilization of two distinct radiation hybrid mapping panels w ith different levels of resolution demonstrated that both genes are ti ghtly linked to the microsatellite markers D5S424, D5S1977, D5S2529 an d D5S2596 (in order of decreasing LOD scores, from 137 for D5S424 to 7 .7 for D5S2596). Physical mapping using yeast artificial chromosomes ( YACs) and inversion field gel electrophoresis demonstrated that they a re maximally separate by 90 kb. If the association of TR and PAR-2 gen es resulted from a relatively recent gene duplication event from a com mon ancestral gene, these observations provide a general framework for the identification of gene transcripts representing alternative prote olytically activated receptors which may be clustered within this regi on of the human genome. These observations are especially relevant giv en recent evidence that murine and human platelets express alternative signalling mechanisms or receptors for thrombin.