help button home button Endocrine Society Endocrinology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Rossant, C. J.
Right arrow Articles by McNulty, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rossant, C. J.
Right arrow Articles by McNulty, S.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*CALCIUM COMPOUNDS
*CALCIUM, ELEMENTAL
Endocrinology Vol. 140, No. 4 1525-1536
Copyright © 1999 by The Endocrine Society

ARTICLES

Corticotropin-Releasing Factor Type 1 and Type 2{alpha} Receptors Regulate Phosphorylation of Calcium/Cyclic Adenosine 3',5'-Monophosphate Response Element-Binding Protein and Activation of p42/p44 Mitogen-Activated Protein Kinase

C. J. Rossant, R. D. Pinnock, J. Hughes, M. D. Hall and S. McNulty

Parke-Davis Neuroscience Research Center, Cambridge, United Kingdom CB2 2QB

Address all correspondence and requests for reprints to: Dr. S. McNulty, Parke-Davis Neuroscience Research Center, Robinson Way, Cambridge, United Kingdom CB2 2QB. E-mail: shaun.mcnulty{at}wl.com

CRF exerts a key neuroregulatory control on the function of the hypothalamic-pituitary-adrenal axis. These effects are thought to be mediated primarily through activation of Gs-coupled plasma membrane receptors. In the present study, we investigated the effects of activation of CRF receptors by sauvagine on signaling pathways that converge on phosphorylation of the transcription factor calcium/cAMP response element-binding protein (CREB). Studies were undertaken using CHO cell lines transfected with either rat CRF-1 or CRF-2{alpha} receptors. Signaling pathways were investigated using immunocytochemical, Western blot, and imaging techniques. Treatment with sauvagine increased phosphorylation of p42/p44, but not of p38 or stress-activated protein kinase (SAPK)/JUN N-terminal kinase (JNK) mitogen-activated protein (MAP) kinases correlating with increased p42/p44 MAP kinase activity. Mobilization of intracellular Ca2+ stores was observed in cells treated with high concentrations (100 nM, 1 µM) of sauvagine. A time- and dose-dependent increase in phosphorylation of the transcription factor CREB was observed in cultures treated with sauvagine. Phosphorylation of CREB occurred at lower concentrations of sauvagine than those required to mobilize intracellular calcium stores, and phosphorylation was not blocked by the mitogen-activated protein kinase kinase inhibitor PD98059 at a concentration (1 µM) that fully inhibited phosphorylation of MAP kinase. Cotreatment of cultures with the protein kinase A inhibitor H89 (10 µM) blocked fully the stimulatory actions of sauvagine (0.1 nM, 1 nM) on phosphorylation of CREB, but not those on phosphorylation of MAP kinase. Phosphorylation of MAP kinase was partially blocked by the phosphoinositide 3-kinase inhibitor LY294002 (5 µM) and by the phosphoinositide-phospholipase C inhibitor U73122 (10 µM). These data demonstrate that cAMP-, Ca2+-, and MAP kinase-dependent signaling pathways are activated by stimulation of CRF-1 and CRF-2{alpha} receptors. However, in these cells, only protein kinase A-dependent pathways contribute significantly to enhanced phosphorylation of CREB. These represent the first reported observations of CRF receptor-mediated phosphorylation of the transcription factor CREB and activation of MAP kinase signal transduction pathways.




This article has been cited by other articles:


Home page
 EndocrinologyHome page
C. Chandras, Y. Koutmani, E. Kokkotou, C. Pothoulakis, and K. P. Karalis
Activation of Phosphatidylinositol 3-Kinase/Protein Kinase B by Corticotropin-Releasing Factor in Human Monocytes
Endocrinology, October 1, 2009; 150(10): 4606 - 4614.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
R. Hanstein, J. Trotter, C. Behl, and A. B. Clement
Increased Connexin 43 Expression as a Potential Mediator of the Neuroprotective Activity of the Corticotropin-Releasing Hormone
Mol. Endocrinol., September 1, 2009; 23(9): 1479 - 1493.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
S. V. Wu, P.-q. Yuan, L. Wang, Y. L. Peng, C.-Y. Chen, and Y. Tache
Identification and Characterization of Multiple Corticotropin-Releasing Factor Type 2 Receptor Isoforms in the Rat Esophagus
Endocrinology, April 1, 2007; 148(4): 1675 - 1687.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
J. A. Ralph, D. Zocco, B. Bresnihan, O. FitzGerald, A. N. McEvoy, and E. P. Murphy
A Role for Type 1{alpha} Corticotropin-Releasing Hormone Receptors in Mediating Local Changes in Chronically Inflamed Tissue
Am. J. Pathol., March 1, 2007; 170(3): 1121 - 1133.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
E. W. Hillhouse and D. K. Grammatopoulos
The Molecular Mechanisms Underlying the Regulation of the Biological Activity of Corticotropin-Releasing Hormone Receptors: Implications for Physiology and Pathophysiology
Endocr. Rev., May 1, 2006; 27(3): 260 - 286.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
A. S. L. Chan and Y. H. Wong
Gq-Mediated Activation of c-Jun N-Terminal Kinase by the Gastrin-Releasing Peptide-Preferring Bombesin Receptor Is Inhibited upon Costimulation of the Gs-Coupled Dopamine D1 Receptor in COS-7 Cells
Mol. Pharmacol., November 1, 2005; 68(5): 1354 - 1364.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
C. Benou, Y. Wang, J. Imitola, L. VanVlerken, C. Chandras, K. P. Karalis, and S. J. Khoury
Corticotropin-Releasing Hormone Contributes to the Peripheral Inflammatory Response in Experimental Autoimmune Encephalomyelitis
J. Immunol., May 1, 2005; 174(9): 5407 - 5413.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
A. Chen, M. Perrin, B. Brar, C. Li, P. Jamieson, M. DiGruccio, K. Lewis, and W. Vale
Mouse Corticotropin-Releasing Factor Receptor Type 2{alpha} Gene: Isolation, Distribution, Pharmacological Characterization and Regulation by Stress and Glucocorticoids
Mol. Endocrinol., February 1, 2005; 19(2): 441 - 458.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
P. J. Peeters, H. W. Gohlmann, I. Van den Wyngaert, S. M. Swagemakers, L. Bijnens, S. U. Kass, and T. Steckler
Transcriptional Response to Corticotropin-Releasing Factor in AtT-20 Cells
Mol. Pharmacol., November 1, 2004; 66(5): 1083 - 1092.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
A. S. Kreibich and J. A. Blendy
cAMP Response Element-Binding Protein Is Required for Stress But Not Cocaine-Induced Reinstatement
J. Neurosci., July 28, 2004; 24(30): 6686 - 6692.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
B. K. Brar, A. Chen, M. H. Perrin, and W. Vale
Specificity and Regulation of Extracellularly Regulated Kinase1/2 Phosphorylation through Corticotropin-Releasing Factor (CRF) Receptors 1 and 2{beta} by the CRF/Urocortin Family of Peptides
Endocrinology, April 1, 2004; 145(4): 1718 - 1729.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
B. K. Brar, A. K. Jonassen, E. M. Egorina, A. Chen, A. Negro, M. H. Perrin, O. D. Mjos, D. S. Latchman, K.-F. Lee, and W. Vale
Urocortin-II and Urocortin-III Are Cardioprotective against Ischemia Reperfusion Injury: An Essential Endogenous Cardioprotective Role for Corticotropin Releasing Factor Receptor Type 2 in the Murine Heart
Endocrinology, January 1, 2004; 145(1): 24 - 35.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
A. M. Khan and A. G. Watts
Intravenous 2-Deoxy-D-Glucose Injection Rapidly Elevates Levels of the Phosphorylated Forms of p44/42 Mitogen-Activated Protein Kinases (Extracellularly Regulated Kinases 1/2) in Rat Hypothalamic Parvicellular Paraventricular Neurons
Endocrinology, January 1, 2004; 145(1): 351 - 359.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
F. Sananbenesi, A. Fischer, C. Schrick, J. Spiess, and J. Radulovic
Mitogen-Activated Protein Kinase Signaling in the Hippocampus and Its Modulation by Corticotropin-Releasing Factor Receptor 2: A Possible Link between Stress and Fear Memory
J. Neurosci., December 10, 2003; 23(36): 11436 - 11443.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
R. T. Hinkle, E. Donnelly, D. B. Cody, S. Samuelsson, J. S. Lange, M. B. Bauer, M. Tarnopolsky, R. J. Sheldon, S. C. Coste, E. Tobar, et al.
Activation of the CRF 2 receptor modulates skeletal muscle mass under physiological and pathological conditions
Am J Physiol Endocrinol Metab, October 1, 2003; 285(4): E889 - E898.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
C. Li, P. Chen, J. Vaughan, A. Blount, A. Chen, P. M. Jamieson, J. Rivier, M. S. Smith, and W. Vale
Urocortin III Is Expressed in Pancreatic {beta}-Cells and Stimulates Insulin and Glucagon Secretion
Endocrinology, July 1, 2003; 144(7): 3216 - 3224.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
K. Kageyama and T. Suda
Urocortin-Related Peptides Increase Interleukin-6 Output via Cyclic Adenosine 5'-Monophosphate-Dependent Pathways in A7r5 Aortic Smooth Muscle Cells
Endocrinology, June 1, 2003; 144(6): 2234 - 2241.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
Y. Huang, F. L. Chan, C.-W. Lau, S.-Y. Tsang, Z.-Y. Chen, G.-W. He, and X. Yao
Roles of cyclic AMP and Ca2+-activated K+ channels in endothelium-independent relaxation by urocortin in the rat coronary artery
Cardiovasc Res, March 1, 2003; 57(3): 824 - 833.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. Dermitzaki, C. Tsatsanis, A. Gravanis, and A. N. Margioris
Corticotropin-releasing Hormone Induces Fas Ligand Production and Apoptosis in PC12 Cells via Activation of p38 Mitogen-activated Protein Kinase
J. Biol. Chem., March 29, 2002; 277(14): 12280 - 12287.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
D. A. Schreihofer, E. M. Resnick, V. Y. Lin, and M. A. Shupnik
Ligand-Independent Activation of Pituitary ER: Dependence on PKA-Stimulated Pathways
Endocrinology, August 1, 2001; 142(8): 3361 - 3368.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
A. SLOMINSKI, J. WORTSMAN, A. PISARCHIK, B. ZBYTEK, E. A. LINTON, J. E. MAZURKIEWICZ, and E. T. WEI
Cutaneous expression of corticotropin-releasing hormone (CRH), urocortin, and CRH receptors
FASEB J, August 1, 2001; 15(10): 1678 - 1693.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
S. Kuroda, N. Schweighofer, and M. Kawato
Exploration of Signal Transduction Pathways in Cerebellar Long-Term Depression by Kinetic Simulation
J. Neurosci., August 1, 2001; 21(15): 5693 - 5702.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
D. K. Grammatopoulos, H. S. Randeva, M. A. Levine, E. S. Katsanou, and E. W. Hillhouse
Urocortin, but Not Corticotropin-Releasing Hormone (CRH), Activates the Mitogen-Activated Protein Kinase Signal Transduction Pathway in Human Pregnant Myometrium: An Effect Mediated via R1{{alpha}} and R2{beta} CRH Receptor Subtypes and Stimulation of Gq-Proteins
Mol. Endocrinol., December 1, 2000; 14(12): 2076 - 2091.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
B. K. Brar, A. K. Jonassen, A. Stephanou, G. Santilli, J. Railson, R. A. Knight, D. M. Yellon, and D. S. Latchman
Urocortin Protects against Ischemic and Reperfusion Injury via a MAPK-dependent Pathway
J. Biol. Chem., March 17, 2000; 275(12): 8508 - 8514.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. D. Ebert, C. Wechselberger, S. Frank, B. Wallace-Jones, M. Seno, I. Martinez-Lacaci, C. Bianco, M. De Santis, H. K. Weitzel, and D. S. Salomon
Cripto-1 Induces Phosphatidylinositol 3'-Kinase-dependent Phosphorylation of AKT and Glycogen Synthase Kinase 3{beta} in Human Cervical Carcinoma Cells
Cancer Res., September 1, 1999; 59(18): 4502 - 4505.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 1999 by The Endocrine Society