Distinct PAR/IQGAP expression patterns during murine development: implications for thrombin-associated cytoskeletal reorganization.

Thrombin has a critical role in many adult and embryologic cellular processes, exerting its effects through two high-affinity thrombin receptor systems: protease-activated receptor 1 (PAR1) and the PAR3/PAR4 system. Both hPAR1 and hPAR3 are coclustered in the human genome, with hPAR3 encompassed within hIQGAP2, a putative GTPase activating protein with actin polymerizing functions linked to cytoskeletal reorganization. Since hPARs colocalize with hIQGAP2 in the human genome and function coordinately with this protein in platelet thrombin signaling pathways, we have further characterized these genes in developing embryonic and adult tissues. We confirmed the presence of a mIQGAP2/ mPAR gene cluster on murine Chromosome 13 and showed it to be organized similarly to that in humans, except that murine PAR3 is translated off the forward (sense) strand. Northern analysis demonstrated limited mPAR3 expression in adult tissues, although its expression during embryogenesis was evident at E15 in cartilage, brain, and keratinocytes. mIQGAPs 1 and 2 had congruent expression patterns in 11 of 15 adult tissues studied. In contrast, whole embryos demonstrated predominant mIQGAP1 expression starting at E7 and evident to E17. In situ hybridization of whole embryos (E9-E16) demonstrated distinct patterns of tissue-dependent mIQGAP1/ mIQGAP2 expression. Concordant expression (absence or presence) of mPAR1 with either mIQGAP1 or mIQGAP2 was seen in the majority (12 of 15) of adult tissues studied. Similarly, there was no evidence for mPAR3 expression during embryogenesis in the absence of either mIQGAP1 or mIQGAP2. These data provide a panoramic survey of PAR/ IQGAP expression as an initial approach to dissect thrombin signaling pathways linked to cytoskeletal reorganization.