Differential regulation of CREB and ERK phosphorylation through corticotropin-releasing factor receptors type 1 and 2 in AtT-20 and A7r5 cells.
The corticotropin-releasing factor (CRF) family of peptides generally exerts its biological actions by binding to two major subtypes of CRF receptors: CRF receptor type 1 (CRF1 receptor) and CRF receptor type 2 (CRF2 receptor). In this study, we investigated the mechanism by which three ligands altered phosphorylation of CREB and ERK 1/2, using AtT-20 cells (expressing CRF1 receptor) and A7r5 cells (expressing CRF2 receptor). Incubation with 100 nM of CRF, urocortin 1 (UCN 1), or UCN 2 increased CREB phosphorylation. The protein kinase A pathway was involved in the CRF- or UCN-mediated increase in CREB phosphorylation in both cell lines. Bisindolylmaleimide partially inhibited the CRF-mediated increase in CREB phosphorylation, but only in AtT-20 cells, suggesting that the protein kinase C pathway is involved in regulation of CREB phosphorylation via CRF1 receptor but not CRF2 receptor. CRF increased ERK phosphorylation in AtT-20 cells, whereas the UCNs decreased it in A7r5 cells. Bisindolylmaleimide partially inhibited the UCN-mediated decrease in ERK phosphorylation in A7r5 cells, suggesting that the protein kinase C pathway is partially involved in CRF2 receptor signal transduction. In AtT-20 cells, the mitogen-activated protein kinase kinase pathway regulated ERK phosphorylation following CRF1 receptor activation. These findings suggest differential regulation of CREB and ERK 1/2 phosphorylation through CRF receptors.
Kageyama
Kazunori
K
Department of Endocrinology, Metabolism and Infectious Diseases, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, Japan. kkageyama@hkg.odn.ne.jp
Hanada
Komaki
K
Moriyama
Takako
T
Imaizumi
Tadaatsu
T
Satoh
Kei
K
Suda
Toshihiro
T
D000818:Animals; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D010902:Pituitary Gland / Q000187:drug effects* / Q000473:pathology; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D054832:Urocortins; D000099052:CRF Receptor, Type 1
C101531:CRF receptor type 2; D017362:Cyclic AMP Response Element-Binding Protein; D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C088060:bisindolylmaleimide