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J. Biol. Chem., Vol. 269, Issue 40, 24557-24563, 10, 1994
H Ali, RM Richardson, ED Tomhave, RA DuBose, B Haribabu and R Snyderman
Platelet activating factor (PAF) interacts with cell surface receptors to
mediate inflammatory responses. To determine the mechanisms of PAF receptor
regulation, we constructed epitope-tagged human PAF receptor cDNA (ET-PAFR)
and generated stable transfectants in a rat basophilic cell line (RBL-2H3
cells). The expressed receptors displayed ligand binding and functional
properties similar to the native receptors in neutrophils. PAF-stimulated
intracellular Ca2+ mobilization was not inhibited by pertussis toxin (PTx),
whereas phosphoinositide hydrolysis and secretion were blocked by
approximately 40%. The PTx-resistant secretion mediated by PAF was,
however, inhibited by guanosine 5'-O-(2- thio-diphosphate) in permeabilized
RBL-2H3 cells, indicating a role for PTx-insensitive G protein. In contrast
to the PAF receptor, responses mediated by formylpeptide and C5a
chemoattractants were inhibited by PTx. PAF stimulated a dose- and
time-dependent phosphorylation of its receptor. ET-PAFR was also
phosphorylated by phorbol 12-myristate 13- acetate (PMA) and dibutyryl
cyclic AMP. Staurosporine caused complete inhibition of ET-PAFR
phosphorylation by PMA but only partial inhibition by PAF. Receptor
phosphorylation by PAF and PMA correlated with desensitization as measured
by a decrease in both PAF-stimulated GTPase activity in membranes and Ca2+
mobilization in intact cells. Phosphorylation of ET-PAFR by dibutyryl
cyclic AMP was not, however, associated with desensitization. These data
demonstrate that a single PAF receptor population interacts with multiple G
proteins to mediate its biological responses. Moreover, ET-PAFR, unlike the
formylpeptide or C5a receptors, is phosphorylated by at least three kinases
(most likely protein kinases A and C and a receptor kinase). The functional
consequences of cellular activation by various chemoattractants may depend
upon the G protein to which their receptor is coupled.
Regulation of stably transfected platelet activating factor receptor in RBL-2H3 cells. Role of multiple G proteins and receptor phosphorylation
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
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H. Ali, I. Fisher, B. Haribabu, R. M. Richardson, and R. Snyderman Role of Phospholipase Cbeta 3 Phosphorylation in the Desensitization of Cellular Responses to Platelet-activating Factor J. Biol. Chem., May 2, 1997; 272(18): 11706 - 11709. [Abstract] [Full Text] [PDF]
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 D. Stengel, M. Antonucci, M. Arborati, D. Hourton, S. Griglio, M. J. Chapman, and E. Ninio Expression of the PAF Receptor in Human Monocyte–Derived Macrophages Is Downregulated by Oxidized LDL: Relevance to the Inflammatory Phase of Atherogenesis Arterioscler. Thromb. Vasc. Biol., May 1, 1997; 17(5): 954 - 962. [Abstract] [Full Text]
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I. Ishii, T. Izumi, H. Tsukamoto, H. Umeyama, M. Ui, and T. Shimizu Alanine Exchanges of Polar Amino Acids in the Transmembrane Domains of a Platelet-activating Factor Receptor Generate Both Constitutively Active and Inactive Mutants J. Biol. Chem., March 21, 1997; 272(12): 7846 - 7854. [Abstract] [Full Text] [PDF]
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R. M. Richardson, B. Haribabu, H. Ali, and R. Snyderman Cross-desensitization Among Receptors for Platelet Activating Factor and Peptide Chemoattractants. EVIDENCE FOR INDEPENDENT REGULATORY PATHWAYS J. Biol. Chem., November 8, 1996; 271(45): 28717 - 28724. [Abstract] [Full Text] [PDF]
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J.-L. Parent, C. L. Gouill, E. Escher, and M. Rola-Pleszczynski Identification of Transmembrane Domain Residues Determinant in the Structure-Function Relationship of the Human Platelet-activating Factor Receptor by Site-directed Mutagenesis J. Biol. Chem., September 20, 1996; 271(38): 23298 - 23303. [Abstract] [Full Text] [PDF]
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J.-L. Parent, C. Le Gouill, A. J. de Brum-Fernandes, M. Rola-Pleszczynski, and J. Stanková Mutations of Two Adjacent Amino Acids Generate Inactive and Constitutively Active Forms of the Human Platelet-activating Factor Receptor J. Biol. Chem., April 5, 1996; 271(14): 7949 - 7955. [Abstract] [Full Text] [PDF]
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A. B. Tobin, B. Keys, and S. R. Nahorski Identification of a Novel Receptor Kinase That Phosphorylates a Phospholipase C-linked Muscarinic Receptor J. Biol. Chem., February 16, 1996; 271(7): 3907 - 3916. [Abstract] [Full Text] [PDF]
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H. Ali, E. D. Tomhave, R. M. Richardson, B. Haribabu, and R. Snyderman Thrombin Primes Responsiveness of Selective Chemoattractant Receptors at a Site Distal to G Protein Activation J. Biol. Chem., February 9, 1996; 271(6): 3200 - 3206. [Abstract] [Full Text] [PDF]
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R. M. Richardson, H. Ali, E. D. Tomhave, B. Haribabu, and R. Snyderman Cross-desensitization of Chemoattractant Receptors Occurs at Multiple Levels J. Biol. Chem., November 17, 1995; 270(46): 27829 - 27833. [Abstract] [Full Text] [PDF]
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C. G.ía Rodríguez, D. R. Cundell, E. I. Tuomanen, L. F. Kolakowski , Jr., C. Gerard, and N. P. Gerard The Role of N-Glycosylation for Functional Expression of the Human Platelet-activating Factor Receptor J. Biol. Chem., October 20, 1995; 270(42): 25178 - 25184. [Abstract] [Full Text] [PDF]
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 H. Tang, H. Shirai, and T. Inagami Inhibition of Protein Kinase C Prevents Rapid Desensitization of Type 1B Angiotensin II Receptor Circ. Res., August 1, 1995; 77(2): 239 - 248. [Abstract] [Full Text]
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