Source:http://linkedlifedata.com/resource/pubmed/id/10644756
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
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| pubmed:dateCreated |
2000-2-29
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| pubmed:abstractText |
Growth hormone (GH) regulates body growth and metabolism. GH exerts its biological action by stimulating JAK2, a GH receptor (GHR)-associated tyrosine kinase. Activated JAK2 phosphorylates itself and GHR, thus initiating multiple signaling pathways. In this work, we demonstrate that platelet-derived growth factor (PDGF) and lysophosphatidic acid (LPA) down-regulate GH signaling via a protein kinase C (PKC)-dependent pathway. PDGF substantially reduces tyrosyl phosphorylation of JAK2 induced by GH but not interferon-gamma or leukemia inhibitory factor. PDGF, but not epidermal growth factor, decreases tyrosyl phosphorylation of GHR (by approximately 90%) and the amount of both total cellular GHR (by approximately 80%) and GH binding (by approximately 70%). The inhibitory effect of PDGF on GH-induced tyrosyl phosphorylation of JAK2 and GHR is abolished by depletion of 4beta-phorbol 12-myristate 13-acetate (PMA)-sensitive PKCs with chronic PMA treatment and is severely inhibited by GF109203X, an inhibitor of PKCs. In contrast, extracellular signal-regulated kinases 1 and 2 and phosphatidylinositol 3-kinase appear not to be involved in this inhibitory effect of PDGF. LPA, a known activator of PKC, also inhibits GH-induced tyrosyl phosphorylation of JAK2 and GHR and reduces the number of GHR. We propose that ligands that activate PKC, including PDGF, LPA, and PMA, down-regulate GH signaling by decreasing the number of cell surface GHR through promoting GHR internalization and degradation and/or cleavage of membrane GHR and release of the extracellular domain of GHR.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Growth Hormone,
http://linkedlifedata.com/resource/pubmed/chemical/JAK2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Jak2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Janus Kinase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Lysophospholipids,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Platelet-Derived Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jan
|
| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
28
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| pubmed:volume |
275
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
2885-92
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| pubmed:dateRevised |
2010-11-18
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| pubmed:meshHeading |
pubmed-meshheading:10644756-3T3 Cells,
pubmed-meshheading:10644756-Animals,
pubmed-meshheading:10644756-Down-Regulation,
pubmed-meshheading:10644756-Enzyme Activation,
pubmed-meshheading:10644756-Growth Hormone,
pubmed-meshheading:10644756-Humans,
pubmed-meshheading:10644756-Janus Kinase 2,
pubmed-meshheading:10644756-Lysophospholipids,
pubmed-meshheading:10644756-Mice,
pubmed-meshheading:10644756-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:10644756-Phosphorylation,
pubmed-meshheading:10644756-Platelet-Derived Growth Factor,
pubmed-meshheading:10644756-Protein Kinase C,
pubmed-meshheading:10644756-Protein-Tyrosine Kinases,
pubmed-meshheading:10644756-Proto-Oncogene Proteins,
pubmed-meshheading:10644756-Signal Transduction,
pubmed-meshheading:10644756-Tetradecanoylphorbol Acetate,
pubmed-meshheading:10644756-Tyrosine
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| pubmed:year |
2000
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| pubmed:articleTitle |
Platelet-derived growth factor and lysophosphatidic acid inhibit growth hormone binding and signaling via a protein kinase C-dependent pathway.
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| pubmed:affiliation |
Department of Physiology, University of Michigan Medical School, Ann Arbor, Michigan 48109-0622, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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