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rdf:type |
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lifeskim:mentions |
umls-concept:C0001455,
umls-concept:C0006675,
umls-concept:C0010132,
umls-concept:C0010531,
umls-concept:C0205263,
umls-concept:C0752312,
umls-concept:C1314939,
umls-concept:C1366488,
umls-concept:C1367453,
umls-concept:C1370600,
umls-concept:C1417836,
umls-concept:C1704259,
umls-concept:C1705987,
umls-concept:C1707524,
umls-concept:C1879547
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pubmed:issue |
7
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pubmed:dateCreated |
2002-6-28
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pubmed:abstractText |
Nur factors are critical for proopiomelanocortin (POMC) induction by CRH in corticotrophs, but the pathways linking CRH to Nur are unknown. In this study we show that in AtT-20 corticotrophs CRH and cAMP induce Nur77 and Nurr1 expression and transcription at the NurRE site by protein kinase A (PKA) and calcium-dependent and -independent mechanisms. Calcium pathways depend on calmodulin kinase II (CAMKII) activity, and calcium-independent pathways are accounted for in part by MAPK activation (Rap1/B-Raf/MAPK-ERK kinase/ERK1/2), demonstrated by the use of molecular and pharmacological tools. AtT-20 corticotrophs express B-Raf, as do other cells in which cAMP stimulates MAPK. CRH/cAMP stimulated ERK2 activity and increased transcriptional activity of a Gal4-Elk1 protein, which was blocked by overexpression of dominant negative mutants and kinase inhibitors and stimulated by expression of B-Raf. The MAPK kinase inhibitors did not affect Nur77 and Nurr1 mRNA induction but blocked CRH or cAMP-stimulated Nur transcriptional activity. Moreover, MAPK stimulated phosphorylation and transactivation of Nur77. The functional impact of these pathways was confirmed at the POMC promoter. In conclusion, in AtT-20 corticotrophs the CRH/cAMP signaling that leads to Nur77/Nurr1 mRNA induction and transcriptional activation, and thus POMC expression, is dependent on protein kinase A and involves calcium/calmodulin kinase II (Nur induction/activation) and MAPK calcium-dependent and -independent (Nur phosphorylation-activation) pathways.
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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/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channel Blockers,
http://linkedlifedata.com/resource/pubmed/chemical/Corticotropin-Releasing Hormone,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Elk1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Nifedipine,
http://linkedlifedata.com/resource/pubmed/chemical/Nr4a1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Nr4a2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Receptor Subfamily 4...,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Receptor Subfamily 4...,
http://linkedlifedata.com/resource/pubmed/chemical/Pro-Opiomelanocortin,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Steroid,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/ets-Domain Protein Elk-1
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0888-8809
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
16
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1638-51
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12089357-Animals,
pubmed-meshheading:12089357-Calcium,
pubmed-meshheading:12089357-Calcium Channel Blockers,
pubmed-meshheading:12089357-Cells, Cultured,
pubmed-meshheading:12089357-Corticotropin-Releasing Hormone,
pubmed-meshheading:12089357-Cyclic AMP,
pubmed-meshheading:12089357-Cyclic AMP-Dependent Protein Kinases,
pubmed-meshheading:12089357-DNA-Binding Proteins,
pubmed-meshheading:12089357-MAP Kinase Signaling System,
pubmed-meshheading:12089357-Mice,
pubmed-meshheading:12089357-Mutation,
pubmed-meshheading:12089357-Nifedipine,
pubmed-meshheading:12089357-Nuclear Receptor Subfamily 4, Group A, Member 1,
pubmed-meshheading:12089357-Nuclear Receptor Subfamily 4, Group A, Member 2,
pubmed-meshheading:12089357-Phosphorylation,
pubmed-meshheading:12089357-Pituitary Gland,
pubmed-meshheading:12089357-Pro-Opiomelanocortin,
pubmed-meshheading:12089357-Promoter Regions, Genetic,
pubmed-meshheading:12089357-Proto-Oncogene Proteins,
pubmed-meshheading:12089357-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:12089357-Receptors, Steroid,
pubmed-meshheading:12089357-Response Elements,
pubmed-meshheading:12089357-Signal Transduction,
pubmed-meshheading:12089357-Transcription, Genetic,
pubmed-meshheading:12089357-Transcription Factors,
pubmed-meshheading:12089357-ets-Domain Protein Elk-1
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pubmed:year |
2002
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pubmed:articleTitle |
Activation and induction of NUR77/NURR1 in corticotrophs by CRH/cAMP: involvement of calcium, protein kinase A, and MAPK pathways.
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pubmed:affiliation |
Laboratorio de Fisiología y Biología Molecular, Departamento de Biología, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, 1428 Buenos Aires, Argentina.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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