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Titolo:
ACTIVATION OF P-2Y2 RECEPTORS BY UTP AND ATP STIMULATES MITOGEN-ACTIVATED KINASE-ACTIVITY THROUGH A PATHWAY THAT INVOLVES RELATED ADHESION FOCAL TYROSINE KINASE AND PROTEIN-KINASE-C
Autore:
SOLTOFF SP; AVRAHAM H; AVRAHAM S; CANTLEY LC;
Indirizzi:
HARVARD UNIV,BETH ISRAEL MED CTR,DIV SIGNAL TRANSDUCT,HARVARD INST MED,DEPT MED,SCH MED BOSTON MA 02215 HARVARD UNIV,SCH MED,BETH ISRAEL MED CTR,DEPT MED,DIV HEMATOL ONCOL BOSTON MA 02215 HARVARD UNIV,SCH MED,DEPT CELL BIOL BOSTON MA 02215
Titolo Testata:
The Journal of biological chemistry
fascicolo: 5, volume: 273, anno: 1998,
pagine: 2653 - 2660
SICI:
0021-9258(1998)273:5<2653:AOPRBU>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
PC12 CELLS; EXTRACELLULAR ATP; GROWTH-FACTOR; EPITHELIAL-CELLS; PHOSPHOLIPASE-C; SIGNAL-TRANSDUCTION; CALCIUM INFLUX; SUBSTANCE-P; MAP KINASE; DELTA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
46
Recensione:
Indirizzi per estratti:
Citazione:
S.P. Soltoff et al., "ACTIVATION OF P-2Y2 RECEPTORS BY UTP AND ATP STIMULATES MITOGEN-ACTIVATED KINASE-ACTIVITY THROUGH A PATHWAY THAT INVOLVES RELATED ADHESION FOCAL TYROSINE KINASE AND PROTEIN-KINASE-C", The Journal of biological chemistry, 273(5), 1998, pp. 2653-2660

Abstract

We examined downstream signaling events that followed the exposure ofPC12 cells to extracellular ATP and UTP, and we compared the effects of these P-2 receptor agonists with those of growth factors and other stimuli, Based on early findings, we focused particular attention on the mitogen-activated protein (MAP) kinase pathway, ATP and/or UTP produced increases in tyrosine phosphorylation of multiple proteins, including p42 MAP (ERK2) kinase, related adhesion focal tyrosine kinase (RAFTK) (PYK2, CAK beta), focal adhesion kinase (FAK), Shc, and protein kinase C delta (PKC delta). MAP (ERK2) kinase activity (quantified by substrate phosphorylation) was increased by UTP, ATP, phorbol la-myristate 13-acetate, ionomycin, and growth factors, UTP and ATP were equipotent (EC50 similar to 25 mu M) in stimulating MAP kinase activity, suggesting that these effects were mediated via the G(i)-linked P-2Y2 (P-2U) receptor. Consistent with this, the UTP-and ATP-promoted activation of MAP kinase was diminished in pertussis toxin-treated cells, Treatment of cells with pertussis toxin also reduced both the UTP-dependentincreases in intracellular calcium ion concentration ([Ca2+](i)) and the tyrosine phosphorylation of RAFTK, Similarly, when [Ca2+](i) elevation was prevented using BAPTA and EGTA, the activation of MAP kinase by UTP and ionomycin was blocked, and the tyrosine phosphorylation of RAFTK was reduced, The UTP-promoted increase in MAP kinase activity was partially reduced in cells in which PKC was down-regulated, suggesting that both PKC-dependent and PKC independent pathways were involved,PKC delta, which increases MAP kinase activity in some systems, became tyrosine-phosphorylated within 15 s of exposure of cells to ATP or UTP; but epidermal growth factor, nerve growth factor, and insulin had little effect, UTP also promoted the association of Shc with Grb2. These results suggest that the P,,, receptor-initiated activation of MAP kinase was dependent on the elevation of [Ca2+](i), involved the recruitment of Shc and Grb2, and was mediated by RAFTK and PKC.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 07/07/20 alle ore 12:56:46