Protein tyrosine phosphorylation and regulation of the receptor for platelet-activating factor in rat Kupffer cells. Effect of sodium vanadate.
Platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine, AGEPC) and sodium vanadate (a phosphotyrosine phosphatase inhibitor) induced a time- and concentration-dependent increase in phosphotyrosine in several proteins and stimulated prostaglandin (PG) E2 production in cultured rat Kupffer cells. In addition, vanadate induced a decrease in the surface expression of AGEPC receptors and, as a consequence, inhibited AGEPC-stimulated PGE2 production. The vanadate-induced decrease in the surface expression of AGEPC receptors was time- and concentration-dependent and was partially prevented by genistein, a putative tyrosine kinase inhibitor. Upon removal of vanadate from the culture medium and re-incubation of cells in vanadate-free medium, the surface AGEPC receptors were restored within 7 h after the removal of vanadate. Both AGEPC- and vanadate-stimulated PGE2 formation was attenuated by genistein. Thus the present investigation demonstrates that both AGEPC and sodium vanadate stimulate tyrosine phosphorylation of cellular proteins, and vanadate induces a decrease in the number of the surface AGEPC receptors. These results suggest that protein tyrosine phosphorylation may play a role, directly or indirectly, in the regulation of surface expression of AGEPC receptors as well as in PGE2 production in response to vanadate and AGEPC.
Chao
W
W
Department of Biochemistry, University of Texas Health Science Center, San Antonio 78284-7760.
Liu
H
H
Hanahan
D J
DJ
Olson
M S
MS
D000818:Animals; D015232:Dinoprostone / Q000096:biosynthesis; D019833:Genistein; D007529:Isoflavones / Q000494:pharmacology; D007700:Kinetics; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D010972:Platelet Activating Factor / Q000378:metabolism / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism* / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011506:Proteins / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled; D012680:Sensitivity and Specificity; D013268:Stimulation, Chemical; D013696:Temperature; D013997:Time Factors; D014638:Vanadates / Q000494:pharmacology*
D007529:Isoflavones; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011506:Proteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D014638:Vanadates; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D017027:Protein Tyrosine Phosphatases; D015232:Dinoprostone