| A role for PKD1 and PKD3 activation in modulation of calcium oscillations induced by orexin receptor 1 stimulation. | |
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MedLine Citation:
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PMID: 20621130 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The neuropeptides orexin-A/hypocretin-1 (Ox-A) and orexin-B/hypocretin-2 play an important role in the control of energy metabolism via either of two G-protein-coupled receptors, orexin receptor 1 (Ox1R) and 2. Despite its significant physiological functions, signaling via orexin receptors is still poorly characterized. The aim of this study was to improve our understanding of early signaling events triggered by the binding of Ox-A to Ox1R. Using phosphospecific antibodies, we observed that early kinase activation by Ox-A in a HEK293 cell line stably expressing Ox1R (HEKOx1R) included ERK1/2, PKCdelta, and PKD1. Elevation of intracellular Ca(2+) is a well-characterized response to Ox1R activation. Comparison of Ox-A-induced calcium elevation and PKD1 activation demonstrated that both responses are detectable soon after stimulation and increase in a dose-dependent manner, but inhibition of protein kinase C, when low Ox-A concentrations are used, affects them differently. PKD family of protein kinases has 3 members: PKD1, 2, and 3, which are all expressed in HEKOx1R cells. In response to stimulation of the cells with 1nM Ox-A, both PKD1 and PKD3 are activated and increased in the plasma membrane, pointing at a possible role for these kinases in that cell compartment. Overexpression of either kinase-dead PKD1 or kinase-dead PKD3 disrupts Ox-A-induced calcium oscillations demonstrating the functional role of these kinases in modulating physiological responses to Ox-A. |
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Authors:
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Hanna M Peltonen; Karl E O Akerman; Geneviève Bart |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-07-16 |
Journal Detail:
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Title: Biochimica et biophysica acta Volume: 1803 ISSN: 0006-3002 ISO Abbreviation: Biochim. Biophys. Acta Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-08-16 Completed Date: 2010-10-28 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0217513 Medline TA: Biochim Biophys Acta Country: Netherlands |
Other Details:
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Languages: eng Pagination: 1206-12 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier B.V. All rights reserved. |
Affiliation:
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Department of Neurobiology, University of Eastern Finland, Kuopio, Finland. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Blotting, Western Calcium / metabolism* Calcium Signaling / drug effects Cell Line Dose-Response Relationship, Drug Enzyme Activation / drug effects Green Fluorescent Proteins / genetics, metabolism Humans Intracellular Signaling Peptides and Proteins / pharmacology Microscopy, Fluorescence Mitogen-Activated Protein Kinase 1 / metabolism Mitogen-Activated Protein Kinase 3 / metabolism Neuropeptides / pharmacology Phosphorylation / drug effects Protein Kinase C Protein Kinases / genetics, metabolism* Receptors, G-Protein-Coupled / genetics, metabolism* Receptors, Neuropeptide / genetics, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Intracellular Signaling Peptides and Proteins; 0/Neuropeptides; 0/Receptors, G-Protein-Coupled; 0/Receptors, Neuropeptide; 0/orexin receptors; 0/orexins; 147336-22-9/Green Fluorescent Proteins; 7440-70-2/Calcium; EC 2.7.-/Protein Kinases; EC 2.7.1.-/protein kinase C nu; EC 2.7.10.-/protein kinase D; EC 2.7.11.13/Protein Kinase C; EC 2.7.11.24/MAPK1 protein, human; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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