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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6764
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pubmed:dateCreated |
2000-1-10
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pubmed:abstractText |
Cross-communication between different signalling systems allows the integration of the great diversity of stimuli that a cell receives under varying physiological situations. The transactivation of epidermal growth factor receptor (EGFR)-dependent signalling pathways upon stimulation of G-protein-coupled receptors (GPCRs), which are critical for the mitogenic activity of ligands such as lysophosphatidic acid, endothelin, thrombin, bombesin and carbachol, provides evidence for such an interconnected communication network. Here we show that EGFR transactivation upon GPCR stimulation involves proHB-EGF and a metalloproteinase activity that is rapidly induced upon GPCR-ligand interaction. We show that inhibition of proHB-EGF processing blocks GPCR-induced EGFR transactivation and downstream signals. The pathophysiological significance of this mechanism is demonstrated by inhibition of constitutive EGFR activity upon treatment of PC3 prostate carcinoma cells with the metalloproteinase inhibitor batimastat. Together, our results establish a new mechanistic concept for cross-communication among different signalling systems.
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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/ADAM Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/ADAM9 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Bacterial Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/CRM197 (non-toxic variant of...,
http://linkedlifedata.com/resource/pubmed/chemical/Disintegrins,
http://linkedlifedata.com/resource/pubmed/chemical/Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Metalloendopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Precursors,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Muscarinic,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Platelet-Derived Growth...,
http://linkedlifedata.com/resource/pubmed/chemical/heparin-binding EGF-like growth...
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pubmed:status |
MEDLINE
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pubmed:issn |
0028-0836
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
402
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
884-8
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:10622253-ADAM Proteins,
pubmed-meshheading:10622253-Animals,
pubmed-meshheading:10622253-Bacterial Proteins,
pubmed-meshheading:10622253-COS Cells,
pubmed-meshheading:10622253-Cell Line,
pubmed-meshheading:10622253-Disintegrins,
pubmed-meshheading:10622253-Epidermal Growth Factor,
pubmed-meshheading:10622253-GTP-Binding Proteins,
pubmed-meshheading:10622253-Humans,
pubmed-meshheading:10622253-Intercellular Signaling Peptides and Proteins,
pubmed-meshheading:10622253-Membrane Proteins,
pubmed-meshheading:10622253-Metalloendopeptidases,
pubmed-meshheading:10622253-Phosphorylation,
pubmed-meshheading:10622253-Protein Precursors,
pubmed-meshheading:10622253-Protein Processing, Post-Translational,
pubmed-meshheading:10622253-Rats,
pubmed-meshheading:10622253-Receptor, Epidermal Growth Factor,
pubmed-meshheading:10622253-Receptors, Muscarinic,
pubmed-meshheading:10622253-Receptors, Platelet-Derived Growth Factor,
pubmed-meshheading:10622253-Signal Transduction,
pubmed-meshheading:10622253-Transcriptional Activation,
pubmed-meshheading:10622253-Tumor Cells, Cultured
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pubmed:articleTitle |
EGF receptor transactivation by G-protein-coupled receptors requires metalloproteinase cleavage of proHB-EGF.
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pubmed:affiliation |
Department of Molecular Biology, Max-Planck-Institut für Biochemie, Martinsried, Germany.
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pubmed:publicationType |
Journal Article
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