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rdf:type |
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lifeskim:mentions |
umls-concept:C0007634,
umls-concept:C0027930,
umls-concept:C0031715,
umls-concept:C0086597,
umls-concept:C0205263,
umls-concept:C0346647,
umls-concept:C1120843,
umls-concept:C1333928,
umls-concept:C1418600,
umls-concept:C1538716,
umls-concept:C1538717
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pubmed:issue |
2
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pubmed:dateCreated |
2008-1-23
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pubmed:abstractText |
It is widely recognized that Hsp27 is a downstream substrate of the p38 MAPK cascade whereas the role of PKD family members in mediating receptor-stimulated Hsp27 Ser-82 phosphorylation has not been evaluated. Here, we show that neurotensin induced a rapid and striking increase in Hsp27 Ser-82 phosphorylation in PANC-1 cells, which was closely correlated with stimulation of activation loop phosphorylation of PKDs and p38 MAPK Thr180/Tyr182 phosphorylation. Treatment of PANC-1 cells with either the selective PKC inhibitor GF-I or the p38 MAPK inhibitor SB202190 partially reduced neurotensin-induced Hsp27 Ser-82 phosphorylation. However, treatment of the cells with a combination of GF-I and SB202190 virtually abolished neurotensin-induced Hsp27 Ser-82 phosphorylation. Overexpression of PKD in stably transfected PANC-1 cells increased the magnitude and prolonged the duration of Hsp27 Ser-82 phosphorylation in response to neurotensin. Either PKD or PKD2 gene silencing utilizing siRNAs targeting distinct PKD or PKD2 sequences reduced neurotensin-stimulated Hsp27 Ser-82 phosphorylation, but cotransfection of siRNAs targeting both, PKD and PKD2, markedly decreased neurotensin-induced Hsp27 Ser-82 phosphorylation. Knockdown of PKD and PKD2 abolished Hsp27 phosphorylation in cells treated with SB202190. Thus, neurotensin induces Hsp27 Ser-82 phosphorylation through p38 MAPK- and PKC/PKD-dependent pathways in PANC-1 cells. Our results demonstrate, for the first time, that neurotensin induces a striking increase in Hsp27 phosphorylation on Ser-82 in PANC-1 cells through convergent p38 MAPK, PKD, and PKD2 signaling.
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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/Anisomycin,
http://linkedlifedata.com/resource/pubmed/chemical/Heat-Shock Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Neurotensin,
http://linkedlifedata.com/resource/pubmed/chemical/Phorbol 12,13-Dibutyrate,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoserine,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/protein kinase D,
http://linkedlifedata.com/resource/pubmed/chemical/protein kinase D2
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1097-4644
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pubmed:author |
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pubmed:copyrightInfo |
(c) 2007 Wiley-Liss, Inc.
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
103
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
648-62
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:17570131-Anisomycin,
pubmed-meshheading:17570131-Carcinoma, Pancreatic Ductal,
pubmed-meshheading:17570131-Cell Line, Tumor,
pubmed-meshheading:17570131-Heat-Shock Proteins,
pubmed-meshheading:17570131-Humans,
pubmed-meshheading:17570131-MAP Kinase Signaling System,
pubmed-meshheading:17570131-Neoplasm Proteins,
pubmed-meshheading:17570131-Neurotensin,
pubmed-meshheading:17570131-Pancreatic Neoplasms,
pubmed-meshheading:17570131-Phorbol 12,13-Dibutyrate,
pubmed-meshheading:17570131-Phosphorylation,
pubmed-meshheading:17570131-Phosphoserine,
pubmed-meshheading:17570131-Protein Kinase C,
pubmed-meshheading:17570131-Protein Kinase Inhibitors,
pubmed-meshheading:17570131-Protein Kinases,
pubmed-meshheading:17570131-Protein Processing, Post-Translational,
pubmed-meshheading:17570131-RNA, Small Interfering,
pubmed-meshheading:17570131-RNA Interference,
pubmed-meshheading:17570131-Recombinant Fusion Proteins,
pubmed-meshheading:17570131-Signal Transduction,
pubmed-meshheading:17570131-p38 Mitogen-Activated Protein Kinases
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pubmed:year |
2008
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pubmed:articleTitle |
PKD, PKD2, and p38 MAPK mediate Hsp27 serine-82 phosphorylation induced by neurotensin in pancreatic cancer PANC-1 cells.
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pubmed:affiliation |
Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine; CURE: Digestive Diseases Research Center and Molecular Biology Institute, University of California, Los Angeles, California 90095, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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