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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
8
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pubmed:dateCreated |
2002-2-18
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pubmed:abstractText |
Here we demonstrate that phosphorylation of the sphingosine 1-phosphate (SSP) receptor "endothelial differentiation gene 1" (EDG1 or S1P(1)) receptor is increased in response to either SSP or phorbol 12-myristate 13-acetate (PMA) exposure but not lysophosphatidic acid. Phosphoamino acid analysis demonstrated that SSP stimulated the accumulation of phosphoserine and phosphothreonine but not phosphotyrosine. An inhibitor of PMA-stimulated EDG1 phosphorylation failed to block SSP-stimulated phosphorylation. Additionally, removal of 12 amino acids from the carboxyl terminus of EDG1 specifically reduced SSP- but not PMA-stimulated phosphorylation, suggesting that SSP and PMA increase EDG1 phosphorylation via distinct mechanisms. In vitro assays revealed that G-protein-coupled receptor kinase 2 may be at least partially responsible for SSP-stimulated EDG1 phosphorylation observed in intact cells. In addition, phosphorylation by PMA and SSP were associated with a loss of EDG1 from the cell surface by distinct mechanisms. Removal of 12 residues from the carboxyl terminus of EDG1 completely inhibited SSP-mediated internalization, suggesting that this domain dictates susceptibility to receptor internalization while retaining sensitivity to SSP-stimulated phosphorylation. Thus, we conclude that (a) EDG1 phosphorylation and internalization are controlled via independent mechanisms by agonist occupation of the receptor and protein kinase C activation, and (b) although determinants within the receptor's carboxyl-terminal tail conferring EDG1 sensitivity to agonist-mediated internalization and G-protein-coupled receptor kinase phosphorylation exhibit a degree of overlap, the two phenomena are separable.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers,
http://linkedlifedata.com/resource/pubmed/chemical/Green Fluorescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Immediate-Early Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Luminescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoserine,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphotyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, G-Protein-Coupled,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Lysophospholipid,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate,
http://linkedlifedata.com/resource/pubmed/chemical/beta-Adrenergic Receptor Kinases
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
22
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pubmed:volume |
277
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5767-77
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:11741892-Animals,
pubmed-meshheading:11741892-Base Sequence,
pubmed-meshheading:11741892-Cell Line,
pubmed-meshheading:11741892-Cricetinae,
pubmed-meshheading:11741892-Cyclic AMP-Dependent Protein Kinases,
pubmed-meshheading:11741892-DNA Primers,
pubmed-meshheading:11741892-Fibroblasts,
pubmed-meshheading:11741892-Green Fluorescent Proteins,
pubmed-meshheading:11741892-Humans,
pubmed-meshheading:11741892-Immediate-Early Proteins,
pubmed-meshheading:11741892-Kidney,
pubmed-meshheading:11741892-Kinetics,
pubmed-meshheading:11741892-Luminescent Proteins,
pubmed-meshheading:11741892-Phosphorylation,
pubmed-meshheading:11741892-Phosphoserine,
pubmed-meshheading:11741892-Phosphotyrosine,
pubmed-meshheading:11741892-Polymerase Chain Reaction,
pubmed-meshheading:11741892-Protein Kinase C,
pubmed-meshheading:11741892-Protein Transport,
pubmed-meshheading:11741892-Receptors, Cell Surface,
pubmed-meshheading:11741892-Receptors, G-Protein-Coupled,
pubmed-meshheading:11741892-Receptors, Lysophospholipid,
pubmed-meshheading:11741892-Recombinant Fusion Proteins,
pubmed-meshheading:11741892-Tetradecanoylphorbol Acetate,
pubmed-meshheading:11741892-Transfection,
pubmed-meshheading:11741892-beta-Adrenergic Receptor Kinases
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pubmed:year |
2002
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pubmed:articleTitle |
Dual regulation of EDG1/S1P(1) receptor phosphorylation and internalization by protein kinase C and G-protein-coupled receptor kinase 2.
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pubmed:affiliation |
Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, United Kingdom.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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