Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
P2Y(2) nucleotide receptor signaling in human monocytic cells: Activation,desensitization, and coupling to mitogen-activated protein kinases
Autore:
Santiago-Perez, LI; Flores, RV; Santos-Berrios, C; Chorna, NE; Krugh, B; Garrad, RC; Erb, L; Weisman, GA; Gonzalez, FA;
Indirizzi:
Univ Puerto Rico, Dept Chem, Rio Piedras, PR 00931 USA Univ Puerto Rico Rio Piedras PR USA 00931 Chem, Rio Piedras, PR 00931 USA Univ Missouri, Dept Biochem, Columbia, MO USA Univ Missouri Columbia MO USA v Missouri, Dept Biochem, Columbia, MO USA
Titolo Testata:
JOURNAL OF CELLULAR PHYSIOLOGY
fascicolo: 2, volume: 187, anno: 2001,
pagine: 196 - 208
SICI:
0021-9541(200105)187:2<196:PNRSIH>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
G-BETA-GAMMA; AGONIST-INDUCED DESENSITIZATION; MESSENGER-RNA EXPRESSION; FOCAL TYROSINE KINASE; EXTRACELLULAR ATP; PHOSPHATIDYLINOSITOL 3-KINASE; PURINERGIC RECEPTORS; IMMUNE-SYSTEM; OKADAIC ACID; U937;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
54
Recensione:
Indirizzi per estratti:
Indirizzo: Gonzalez, FA Univ Puerto Rico, Dept Chem, POB 23346, Rio Piedras, PR 00931USA Univ Puerto Rico POB 23346 Rio Piedras PR USA 00931 00931 USA
Citazione:
L.I. Santiago-Perez et al., "P2Y(2) nucleotide receptor signaling in human monocytic cells: Activation,desensitization, and coupling to mitogen-activated protein kinases", J CELL PHYS, 187(2), 2001, pp. 196-208

Abstract

Activation of P2Y(2) receptors by extracellular nucleotides has been shownto induce phenotypic differentiation of human promonocytic U937 cells thatis associated with the inflammatory response. The P2Y(2) receptor agonist,UTP, induced the phosphorylation of the MAP kinases MEK1/2 and ERK1/2 in asequential manner, since ERK1/2 phosphorylation was abolished by the MEK1/2 inhibitor PD 098059. Other results indicated that P2Y(2) receptors can couple to MAP kinases via phosphatidylinositol 3-kinase (P13K) and c-src. Accordingly, ERK1/2 phosphorylation induced by UTP was inhibited by the P13K inhibitors, wortmannin and LY294002, and the c-src inhibitors, radicicol andPP2, but not by inhibitors of protein kinase C (PKC). The phosphorylation of ERK1/2 was independent of the ability of P2Y(2) receptors to increase the concentration of intracellular free calcium, since chelation of intracellular calcium by BAPTA did not diminish the phosphorylation of ERK1/2 induced by UTP. A 5-minute treatment with UTP reduced U937 cell responsiveness toa subsequent UTP challenge. UTP-induced desensitization was characterized by an increase in the EC50 for receptor activation (from 0.44 to 9.3 muM) and a dramatic (similar to 75%) decrease in the maximal calcium mobilizationinduced by a supramaximal dose of UTP. Phorbol ester treatment also causedP2Y(2) receptor desensitization (EC50 = 12.3 muM UTP and maximal calcium mobilization reduced by similar to 33%). The protein kinase C inhibitor GF 109203X failed to significantly inhibit the UTP-induced desensitization of the P2Y(2) receptor, whereas the protein phosphatase inhibitor okadaic acid blocked receptor resensitization. Recovery of receptor activity after UTP-induced desensitization was evident in cells treated with agonist for 5 or 30 min. However, P2Y2 receptor activity remained partially desensitized 30 min after pretreatment of cells with UTP for 1 h or longer. This sustained desensitized state correlated with a decrease in P2Y(2) receptor mRNA levels. Desensitization of ERK1/2 phosphorylation was induced by a 5-minute pretreatment with UTP, and cell responsiveness did not return even after a 30-minute incubation of cells in the absence of an agonist. Results suggest thatdesensitization of the P2Y(2) receptor may involve covalent modifications (i.e., receptor phosphorylation) that functionally uncouple the receptor from the calcium signaling pathway, and that transcriptional regulation may play a role in long-term desensitization. Our results indicate that calcium mobilization and ERK1/2 phosphorylation induced by P2Y(2) receptor activation are independent events in U937 monocytes. (C) 2001 Wiley-Liss, Inr.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/04/20 alle ore 00:49:59