P2Y receptors activate MAPK/ ERK through a pathway involving PI3K/ PDK1/PKC-zeta in human vein endothelial cells.
AIMS: In this study we investigated the effects of P2 receptors in the regulation of mitogen-activated protein kinase/extracellular signal-regulated kinase ( MAPK/ ERK) in human umbilical vein endothelial cells (HUVEC). METHODS: Cytosolic Ca(2+) concentration ([Ca(2+)](i)) was measured using fura-2/AM, and MAPK/ ERK phosphorylation using Western blot analysis. RESULTS: ATP, 2-meSATP, UTP and UDP cause a rapid and transitory increase in the phosphorylation of MAPK/ ERK. In contrast, negligible response was seen for a,Beta-meATP, a general P2X receptors agonist. ATP-dependent activation of MAPK/ ERK was prevented by pretreatment of HUVEC with pertussis toxin or MEK inhibitor PD98059. In addition, activation of the MAPK/ ERK cascade by ATP was blocked in cells pretreated with wortmannin and LY294002, but not by U73122, BAPTA or a Ca(2+)-free medium. Furthermore, an inhibition of ATP-dependent MAPK/ ERK phosphorylation was observed in HUVEC pretreated with high doses of GF109203X or myristoylated PKC- zeta pseudosubstrate. Similar results were observed when cells were pretreated with the Src tyrosine kinase inhibitor PP2. However, ATP-stimulated MAPK/ ERK activation was unaffected in cells pretreated with AG1478 or perillic acid. We also found that ATP stimulates both the phosphorylation of 3- phosphoinositide-dependent protein kinase-1 ( PDK1) and its translocation to plasma membrane in a time-dependent manner. CONCLUSION: These observations suggest that the effects mediated by ATP in HUVEC occur via PTX-sensitive G-protein- coupled P2Y receptors through PI3K-dependent mechanisms, in which PDK1 and PKC-zeta are two key molecules within signal cascade leading to MAPK/ ERK activation.[1]References
- P2Y receptors activate MAPK/ERK through a pathway involving PI3K/PDK1/PKC-zeta in human vein endothelial cells. Montiel, M., de la Blanca, E.P., Jiménez, E. Cell. Physiol. Biochem. (2006) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg