Evidence of the Importance of the First Intracellular Loop of Prokineticin Receptor 2 in Receptor Function

Imagem de Miniatura
Arquivos
art_Abreu_Evidence_of_the_Importance_of_the_First_Intracellular_2012.PDF (714.86 KB)
Citações na Scopus
31
Tipo de produção
article
Data de publicação
2012
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
ENDOCRINE SOC
Autores
NOEL, Sekoni D.
XU, Shuyun
CARROLL, Rona S.
KAISER, Ursula B.
Citação
MOLECULAR ENDOCRINOLOGY, v.26, n.8, p.1417-1427, 2012
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Prokineticin receptors (PROKR) are G protein-coupled receptors (GPCR) that regulate diverse biological processes, including olfactory bulb neurogenesis and GnRH neuronal migration. Mutations in PROKR2 have been described in patients with varying degrees of GnRH deficiency and are located in diverse functional domains of the receptor. Our goal was to determine whether variants in the first intracellular loop (ICL1) of PROKR2 (R80C, R85C, and R85H) identified in patients with hypogonadotropic hypogonadism interfere with receptor function and to elucidate the mechanisms of these effects. Because of structural homology among GPCR, clarification of the role of ICL1 in PROKR2 activity may contribute to a better understanding of this domain across other GPCR. The effects of the ICL1 PROKR2 mutations on activation of signal transduction pathways, ligand binding, and receptor expression were evaluated. Our results indicated that the R85C and R85H PROKR2 mutations interfere only modestly with receptor function, whereas the R80C PROKR2 mutation leads to a marked reduction in receptor activity. Cotransfection of wild-type (WT) and R80C PROKR2 showed that the R80C mutant could exert a dominant negative effect on WT PROKR2 in vitro by interfering with WT receptor expression. In summary, we have shown the importance of Arg80 in ICL1 for PROKR2 expression and demonstrate that R80C PROKR2 exerts a dominant negative effect on WT PROKR2. (Molecular Endocrinology 26: 1417-1427, 2012)
Palavras-chave
URI
https://observatorio.fm.usp.br/handle/OPI/5027
Referências
  1. Abreu AP, 2008, J CLIN ENDOCR METAB, V93, P4113, DOI 10.1210/jc.2008-0958
  2. Abreu AP, 2010, NEUROENDOCRINOLOGY, V91, P283, DOI 10.1159/000308880
  3. Arora KK, 1998, J BIOL CHEM, V273, P25581, DOI 10.1074/jbc.273.40.25581
  4. Balasubramanian R, 2011, MOL CELL ENDOCRINOL, V346, P44, DOI 10.1016/j.mce.2011.05.040
  5. Bedecarrats GY, 2003, J CLIN ENDOCR METAB, V88, P834, DOI 10.1210/jc.2002-020806
  6. Canto P, 2009, J ANDROL, V30, P41, DOI 10.2164/jandrol.108.005314
  7. Caronia LM, 2011, NEW ENGL J MED, V364, P215, DOI 10.1056/NEJMoa0911064
  8. Chen JC, 2005, MOL PHARMACOL, V67, P2070, DOI 10.1124/mol.105.011619
  9. Cheng MY, 2006, J COMP NEUROL, V498, P796, DOI 10.1002/cne.21087
  10. Cheng MY, 2002, NATURE, V417, P405, DOI 10.1038/417405a
  11. Clouser CL, 2005, MOL CELL ENDOCRINOL, V235, P11, DOI 10.1016/j.mce.2005.02.005
  12. Cole LW, 2008, J CLIN ENDOCR METAB, V93, P3551, DOI 10.1210/jc.2007-2654
  13. Conn PM, 2009, MOL CELL ENDOCRINOL, V299, P137, DOI 10.1016/j.mce.2008.10.051
  14. Conn PM, 2007, PHARMACOL REV, V59, P225, DOI 10.1124/pr.59.3.2
  15. DAVIDSON JS, 1995, MOL CELL ENDOCRINOL, V107, P241, DOI 10.1016/0303-7207(94)03449-4
  16. Dode C, 2006, PLOS GENET, V2, P1648, DOI 10.1371/journal.pgen.0020175
  17. Duvernay MT, 2009, MOL PHARMACOL, V75, P751, DOI 10.1124/mol.108.051623
  18. Duvernay MT, 2009, TRAFFIC, V10, P552, DOI 10.1111/j.1600-0854.2009.00890.x
  19. Goi T, 2004, CANCER RES, V64, P1906, DOI 10.1158/0008-5472.CAN-3696-2
  20. Hamilton SR, 2007, CURR OPIN BIOTECH, V18, P387, DOI 10.1016/j.copblo.2007.09.001
  21. HART GW, 1979, J BIOL CHEM, V254, P9747
  22. Hu WP, 2007, SLEEP, V30, P247
  23. Kelley LP, 2003, BBA-GEN SUBJECTS, V1621, P192, DOI 10.1016/S0304-4165(03)00059-X
  24. Kleinau G, 2010, PLOS ONE, V5, DOI 10.1371/journal.pone.0009745
  25. LeCouter J, 2003, P NATL ACAD SCI USA, V100, P2685, DOI 10.1073/pnas.0337667100
  26. LeCouter J, 2004, P NATL ACAD SCI USA, V101, P16813, DOI 10.1073/pnas.0407697101
  27. Li JD, 2006, J NEUROSCI, V26, P11615, DOI 10.1523/JNEUROSCI.3679-06.2006
  28. Lin DCH, 2002, J BIOL CHEM, V277, P19276, DOI 10.1074/jbc.M202139200
  29. Lin R, 2002, J BIOL CHEM, V277, P8724, DOI 10.1074/jbc.M110594200
  30. MALEY F, 1989, ANAL BIOCHEM, V180, P195, DOI 10.1016/0003-2697(89)90115-2
  31. Marsango S, 2011, CELL MOL LIFE SCI, V68, P2919, DOI 10.1007/s00018-010-0601-6
  32. Martin C, 2011, ENDOCR REV, V32, P225, DOI 10.1210/er.2010-0007
  33. Masuda Y, 2002, BIOCHEM BIOPH RES CO, V293, P396, DOI 10.1016/S0006-291X(02)00239-5
  34. Matsumoto S, 2006, P NATL ACAD SCI USA, V103, P4140, DOI 10.1073/pnas.0508881103
  35. Monnier C, 2009, HUM MOL GENET, V18, P75, DOI 10.1093/hmg/ddn318
  36. Monnier J, 2008, WORLD J GASTROENTERO, V14, P1182, DOI 10.3748/wjg.14.1182
  37. Ng KL, 2005, SCIENCE, V308, P1923, DOI 10.1126/science.1112103
  38. Ngan ESW, 2008, INT J BIOCHEM CELL B, V40, P1679, DOI 10.1016/j.biocel.2008.03.010
  39. Oldham WM, 2008, NAT REV MOL CELL BIO, V9, P60, DOI 10.1038/nrm2299
  40. Peng Z, 2011, J BIOL CHEM, V286, P16615, DOI 10.1074/jbc.M111.223784
  41. Pitteloud N, 2007, J CLIN INVEST, V117, P457, DOI 10.1172/JCI29884
  42. Prosser HM, 2007, P NATL ACAD SCI USA, V104, P648, DOI 10.1073/pnas.0606884104
  43. Prosser HM, 2007, EUR J NEUROSCI, V26, P3339, DOI 10.1111/j.1460-9568.2007.05958.x
  44. Raivio T, 2012, J CLIN ENDOCR METAB, V97, pE694, DOI 10.1210/jc.2011-2938
  45. Roy S, 2010, ENDOCRINOLOGY, V151, P660, DOI 10.1210/en.2009-0826
  46. Ruiz-Ferrer M, 2011, PLOS ONE, V6, DOI 10.1371/journal.pone.0023475
  47. Sarfati J, 2010, J CLIN ENDOCR METAB, V95, P659, DOI 10.1210/jc.2009-0843
  48. Schwachtgen JL, 1998, J CLIN INVEST, V101, P2540, DOI 10.1172/JCI1404
  49. Serre D, 2008, PLOS GENET, V4, DOI 10.1371/journal.pgen.1000006
  50. Shojaei F, 2007, NATURE, V450, P825, DOI 10.1038/nature06348
  51. Sinisi AA, 2008, HUM REPROD, V23, P2380, DOI 10.1093/humrep/den247
  52. Soga T, 2002, BBA-GENE STRUCT EXPR, V1579, P173, DOI 10.1016/S0167-4781(02)00546-8
  53. Sykiotis GP, 2010, P NATL ACAD SCI USA, V107, P15140, DOI 10.1073/pnas.1009622107
  54. VANKOPPEN CJ, 1990, J BIOL CHEM, V265, P20887
  55. Wess J, 1998, PHARMACOL THERAPEUT, V80, P231, DOI 10.1016/S0163-7258(98)00030-8
  56. Wess J, 1997, FASEB J, V11, P346
  57. Wu V, 1997, J BIOL CHEM, V272, P9037

Coleções
Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - LIM/42