Affiliation:
1. Division of Nephrology and Departments of Medicine and Pharmacology, Vanderbilt University, Nashville, Tennessee 37232;,
2. Department of Chemistry, College of William and Mary, Williamsburg, Virginia 23187;
3. Division of Nephrology and Departments of Medicine and Molecular Physiology and Biophysics, Department of Veterans Affairs Medical Center, Vanderbilt Univesity, Nashville, Tennessee 37232;
Abstract
Cyclooxygenases metabolize arachidonate to five primary prostanoids: PGE2, PGF2α, PGI2, TxA2, and PGD2. These autacrine lipid mediators interact with specific members of a family of distinct G-protein-coupled prostanoid receptors, designated EP, FP, IP, TP, and DP, respectively. Each of these receptors has been cloned, expressed, and characterized. This family of eight prostanoid receptor complementary DNAs encodes seven transmembrane proteins which are typical of G-protein-coupled receptors and these receptors are distinguished by their ligand-binding profiles and the signal transduction pathways activated on ligand binding. Ligand-binding selectivity of these receptors is determined by both the transmembrane sequences and amino acid residues in the putative extracellular-loop regions. The selectivity of interaction between the receptors and G proteins appears to be mediated at least in part by the C-terminal tail region. Each of the EP1, EP3, FP, and TP receptors has alternative splice variants described that alter the coding sequence in the C-terminal intracellular tail region. The C-terminal variants modulate signal transduction, phosphorylation, and desensitization of these receptors, as well as altering agonist-independent constitutive activity.
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