Activation and induction of Nur77/Nurr1 in corticotrophs by CRH/cAMP: Involvement of calcium, protein kinase a, and MAPK pathways

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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)...

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Autor principal: Kovalovsky, D.
Otros Autores: Refojo, D., Liberman, A.C, Hochbaum, D., Pereda, M.P, Coso, O.A, Stalla, G.K, Holsboer, F., Arzt, E.
Formato: Capítulo de libro
Lenguaje:Inglés
Publicado: 2002
Acceso en línea:Registro en Scopus
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Biblioteca Central Dr. Luis F. Leloir (FCEN) de Universidad de Buenos Aires
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024 7 |2 scopus  |a 2-s2.0-0036018997 
024 7 |2 cas  |a Calcium Channel Blockers; Calcium, 7440-70-2; Corticotropin-Releasing Hormone, 9015-71-8; Cyclic AMP, 60-92-4; Cyclic AMP-Dependent Protein Kinases, EC 2.7.1.37; DNA-Binding Proteins; ets-domain protein elk-1; MAP Kinase Signaling System; Nifedipine, 21829-25-4; Nurr1 nuclear receptor; orphan nuclear receptor NGFI-B, 121479-42-3; Pro-Opiomelanocortin, 66796-54-1; Proto-Oncogene Proteins; Transcription Factors 
040 |a Scopus  |b spa  |c AR-BaUEN  |d AR-BaUEN 
030 |a MOENE 
100 1 |a Kovalovsky, D. 
245 1 0 |a Activation and induction of Nur77/Nurr1 in corticotrophs by CRH/cAMP: Involvement of calcium, protein kinase a, and MAPK pathways 
260 |c 2002 
270 1 0 |m Arzt, E.; Fac. de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria (1428), Buenos Aires, Argentina; email: earzt@bg.fcen.uba.ar 
506 |2 openaire  |e Política editorial 
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520 3 |a 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.  |l eng 
593 |a Laboratorio de Fisiología y Biología Molecular, Departamento de Biología, Universidad de Buenos Aires, 1428 Buenos Aires, Argentina 
593 |a Max Planck Institute of Psychiatry, 80804 Munich, Germany 
593 |a Laboratorio de Fisiología y Biología Molecular, Facultad de Ciencias Exactas y Naturales, Ciudad Universitaria (1428), Buenos Aires, Argentina 
690 1 0 |a CORTICOSTEROID RECEPTOR 
690 1 0 |a CYCLIC AMP DEPENDENT PROTEIN KINASE 
690 1 0 |a MITOGEN ACTIVATED PROTEIN KINASE 
690 1 0 |a PROOPIOMELANOCORTIN 
690 1 0 |a PROTEIN KINASE (CALCIUM,CALMODULIN) 
690 1 0 |a ANIMAL CELL 
690 1 0 |a ARTICLE 
690 1 0 |a CELL TYPE 
690 1 0 |a CORTICOTROPIN RELEASE 
690 1 0 |a ENZYME ACTIVATION 
690 1 0 |a ENZYME INDUCTION 
690 1 0 |a GENE OVEREXPRESSION 
690 1 0 |a HYPOTHALAMUS HYPOPHYSIS ADRENAL SYSTEM 
690 1 0 |a NONHUMAN 
690 1 0 |a POINT MUTATION 
690 1 0 |a PRIORITY JOURNAL 
690 1 0 |a PROTEIN PHOSPHORYLATION 
690 1 0 |a STIMULUS RESPONSE 
690 1 0 |a STRESS 
690 1 0 |a TRANSCRIPTION REGULATION 
690 1 0 |a ANIMAL 
690 1 0 |a CALCIUM 
690 1 0 |a CALCIUM CHANNEL BLOCKERS 
690 1 0 |a CELLS, CULTURED 
690 1 0 |a CORTICOTROPIN-RELEASING HORMONE 
690 1 0 |a CYCLIC AMP 
690 1 0 |a CYCLIC AMP-DEPENDENT PROTEIN KINASES 
690 1 0 |a DNA-BINDING PROTEINS 
690 1 0 |a MAP KINASE SIGNALING SYSTEM 
690 1 0 |a MICE 
690 1 0 |a MUTATION 
690 1 0 |a NIFEDIPINE 
690 1 0 |a PHOSPHORYLATION 
690 1 0 |a PITUITARY GLAND 
690 1 0 |a PRO-OPIOMELANOCORTIN 
690 1 0 |a PROMOTER REGIONS (GENETICS) 
690 1 0 |a PROTO-ONCOGENE PROTEINS 
690 1 0 |a RESPONSE ELEMENTS 
690 1 0 |a SIGNAL TRANSDUCTION 
690 1 0 |a SUPPORT, NON-U.S. GOV'T 
690 1 0 |a TRANSCRIPTION FACTORS 
690 1 0 |a TRANSCRIPTION, GENETIC 
690 1 0 |a ANIMALIA 
700 1 |a Refojo, D. 
700 1 |a Liberman, A.C. 
700 1 |a Hochbaum, D. 
700 1 |a Pereda, M.P. 
700 1 |a Coso, O.A. 
700 1 |a Stalla, G.K. 
700 1 |a Holsboer, F. 
700 1 |a Arzt, E. 
773 0 |d 2002  |g v. 16  |h pp. 1638-1651  |k n. 7  |p Mol. Endocrinol.  |x 08888809  |w (AR-BaUEN)CENRE-6153  |t Molecular Endocrinology 
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856 4 0 |u https://doi.org/10.1210/me.16.7.1638  |y DOI 
856 4 0 |u https://hdl.handle.net/20.500.12110/paper_08888809_v16_n7_p1638_Kovalovsky  |y Handle 
856 4 0 |u https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_08888809_v16_n7_p1638_Kovalovsky  |y Registro en la Biblioteca Digital 
961 |a paper_08888809_v16_n7_p1638_Kovalovsky  |b paper  |c PE 
962 |a info:eu-repo/semantics/article  |a info:ar-repo/semantics/artículo  |b info:eu-repo/semantics/publishedVersion 
999 |c 66244 

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