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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1998-11-13
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pubmed:abstractText |
The cAMP-dependent pathway has been long presumed to play a critical role in mediating alpha-melanocyte-stimulating hormone (alpha-MSH)-induced pigmentation, but it has never been demonstrated that this pathway is obligatory. In order to determine whether the cAMP-dependent pathway is required for a alpha-MSH-induced pigmentation, we inhibited the activity of cAMP-dependent protein kinase (PKA), the main kinase mediating in this pathway, by introducing a physiologic cAMP-dependent protein kinase inhibitor (PKI) into S91 murine melanoma cells and then measuring pigment response after alpha-MSH stimulation. Cells were stably transfected either with the pMXX-PKI expression vector that encodes the active part of PKI (the amino terminal 1-31 amino acids) under a metallothionein-inducible promoter and the pSV2-Neo expression vector alone. As expected, treatment of transfected cells with 1 microM CdCl2 for 24 h induced the expression of PKI mRNA in cells transfected with both vectors, but not in cells transfected with the pSV2-Neo expression vector alone. Subsequent treatment of these transfected cells with alpha-MSH for 5-6 days in the continual presence of 1 microM CdCl2 resulted in inhibition of PKA activity by 30-40% in cells expressing PKI. Parallel measurements revealed that alpha-MSH-increased melanin content five- to six-fold in control cells transfected with pSV2-Neo alone, while there was only a two-fold increase in PKI-expressing cells, a 40-50% inhibition in alpha-MSH-induced total melanin content. alpha-MSH-induced tyrosinase activity and tyrosinase mRNA and protein levels measured in parallel were also inhibited by 40-50% in PKI-expressing cells compared to control cells transfected with pSV2-Neo alone. Together, these results demonstrate for the first time that activation of PKA through the cAMP-dependent pathway is required for optimal alpha-MSH-induced pigmentation.
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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/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Monophenol Monooxygenase,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/alpha-MSH,
http://linkedlifedata.com/resource/pubmed/chemical/protein kinase modulator
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0014-4827
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pubmed:author | |
pubmed:copyrightInfo |
Copyright 1998 Academic Press.
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pubmed:issnType |
Print
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pubmed:day |
10
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pubmed:volume |
244
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
117-24
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:9770355-Animals,
pubmed-meshheading:9770355-Carrier Proteins,
pubmed-meshheading:9770355-Cyclic AMP-Dependent Protein Kinases,
pubmed-meshheading:9770355-Enzyme Activation,
pubmed-meshheading:9770355-Genetic Vectors,
pubmed-meshheading:9770355-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:9770355-Melanoma,
pubmed-meshheading:9770355-Mice,
pubmed-meshheading:9770355-Monophenol Monooxygenase,
pubmed-meshheading:9770355-Pigmentation,
pubmed-meshheading:9770355-RNA, Messenger,
pubmed-meshheading:9770355-Transfection,
pubmed-meshheading:9770355-Tumor Cells, Cultured,
pubmed-meshheading:9770355-alpha-MSH
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pubmed:year |
1998
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pubmed:articleTitle |
Activation of cAMP-dependent protein kinase is required for optimal alpha-melanocyte-stimulating hormone-induced pigmentation.
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pubmed:affiliation |
Department of Dermatology, Boston University School of Medicine, 80 East Concord Street, Boston, Massachusetts, 02118, USA.
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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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