Edward J. Goetzl

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The recent identification of the Vzg-1/Edg2 protein as a functional G protein-coupled receptor for lysophosphatidic acid (LPA) has allowed a sequence-based search for new genes that may encode novel subtypes of LPA receptors. A human cDNA encoding a G protein-coupled receptor, designated Edg4, was identified by searching the GenBankTM for homologs of the(More)
The structural similarity of lysosphingolipids to lysophosphatidic acid (LPA) prompted a sequence-based search for lysosphingolipid receptors using cDNA sequence of the Edg2 human LPA receptor. Two closely related G protein-coupled receptors, rat H218 and human Edg3, are highly similar to Edg2. When overexpressed in Jurkat cells, H218 and Edg3 activated(More)
A cDNA homologous to that encoding sheep Edg2 protein was cloned from a human lung cDNA library. The full-length sequence encodes a 364-amino acid protein which belongs to the superfamily of guanine nucleotide-binding (G) protein-coupled receptors. Human Edg2 mRNA is widely distributed in human tissues with the highest abundance in brain. HEK293 cells(More)
FTY720 is an immunosuppressant that reduces circulating levels of naïve lymphocytes by increasing their localization and sequestration in secondary lymphoid organs. It is considered to be an agonist for sphingosine 1-phosphate (S1P) G protein-coupled receptors (GPCRs) after phosphorylation at micromolar concentrations. We now describe its nonagonist and(More)
Sphingosine 1-phosphate (S1P) is a biologically active lysophospholipid that transmits signals through a family of G-protein-coupled receptors to control cellular differentiation and survival, as well as the vital functions of several types of immune cell. In this Review article, we discuss recent results that indicate that S1P and its receptors are(More)
Leukotriene B4, at the same intracutaneous doses as bradykinin, reduced the nociceptive threshold in the rat paw. The mechanism of leukotriene B4-induced hyperalgesia was distinguished from that of the hyperalgesia elicited by prostaglandin E2 and bradykinin by its dependence on polymorphonuclear leukocytes and independence of the cyclooxygenation of(More)
The increase in airway responsiveness induced by O3 exposure in dogs is associated with airway epithelial inflammation, as evidenced by an increase in the number of neutrophils (polymorphonuclear leukocytes) found in epithelial biopsies and in bronchoalveolar lavage fluid. We investigated in 10 healthy, human subjects whether O3-induced hyperresponsiveness(More)
Endothelial differentiation gene (edg)-encoded G protein-coupled receptors (Edg Rs)-1, -3, and -5 bind sphingosine 1-phosphate (S1P), and Edg-2 and -4 bind lysophosphatidic acid (LPA). Edg Rs transduce signals from LPA and S1P that stimulate ras- and rho-dependent cellular proliferation, enhance cellular survival, and suppress apoptosis. That high levels of(More)
BACKGROUND Lysophosphatidic acid (LPA) stimulates ovarian tumor growth at concentrations present in ascitic fluid. Vascular endothelial growth factor (VEGF) stimulates angiogenesis and plays a pivotal role in the formation of ovarian cancer-associated ascites. We examined whether LPA promotes ovarian tumor growth by increasing angiogenesis via VEGF. (More)
Vasoactive intestinal peptide (VIP) and its G protein-coupled receptors, VPAC(1)R and VPAC(2)R, are prominent in the immune system and regulate many aspects of T cell-dependent immunity. In mouse T cells, VPAC(1)R is expressed constitutively, whereas VPAC(2)R is induced by immune stimuli. VPAC(2)R-null (VPAC(2)R(-/-)) mice on a C57BL/6 background are shown(More)