Dominant negative actions of human prostacyclin receptor variant through dimerization: implications for cardiovascular disease.

ABSTRACT:

Objective

Prostacyclin and thromboxane mediate opposing cardiovascular effects through their receptors, the prostacyclin receptor (IP) and thromboxane receptor (TP). Individuals heterozygous for an IP variant, IP(R212C), displayed exaggerated loss of platelet IP responsiveness and accelerated cardiovascular disease. We examined association of IP(R212C) into homo- and heterodimeric receptor complexes and the impact on prostacyclin and thromboxane biology.

Methods and results

Dimerization of the IP, IP(R212C), and TPalpha was examined by bioluminesence resonance energy transfer in transfected HEK293 cells. We observed an equal propensity for formation of IPIP homodimers and IPTPalpha heterodimers. Compared with the IP alone, IP(R212C) displayed reduced cAMP generation and incr

SUBMITTER: Ibrahim S 

PROVIDER: S-EPMC2924460 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature