HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhang, B. Articles by Takeuchi, T. Search for Related Content PubMed PubMed Citation Articles by Zhang, B. Articles by Takeuchi, T. Social Bookmarking                What's this?

Parathyroid Hormone–Related Protein Induces Insulin Expression Through Activation of MAP Kinase–Specific Phosphatase-1 That Dephosphorylates c-Jun NH₂-Terminal Kinase in Pancreatic ß-Cells

¹ Department of Molecular Medicine, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan
² Department of Biochemistry, Mie University School of Medicine, Tsu, Japan

Parathyroid hormone–related protein (PTHrP) increases the content and mRNA level of insulin in a mouse ß-cell line, MIN6, and primary-cultured mouse islets. We examined the mechanism of PTHrP-induced insulin expression. The PTHrP effect was markedly augmented by SB203580, a mitogen-activated protein (MAP) kinase inhibitor, and SB203580 itself increased insulin expression extensively, even without PTHrP. Because SB203580 inhibits both p38 and c-jun NH₂-terminal kinases (JNKs), we investigated the JNK-specific inhibitor SP600125. SP600125 also increased insulin content and its mRNA level. PTHrP induced dephosphorylation of JNK1/2, and PTHrP-induced insulin expression was blocked by a dominant-negative type JNK-APF. We suspected that dual specificity MAP kinase phosphatases (MKPs) may be involved in the PTHrP-induced insulin expression by inactivating JNK1/2. MIN6 cells contained at least five MKPs, among which only MKP-1 was inducible by PTHrP. PTHrP-induced insulin expression was blocked by the MKP-1 expression inhibitor Ro-31-8220, indicating that the PTHrP effect is mediated by MKP-1. Indeed, adenoviral MKP-1 expression increased insulin expression by decreasing a phosphorylation form of JNKs and a resulting phosphorylated form of c-jun in MIN6 cells. The phosphorylated form of c-jun is known to repress cAMP-dependent insulin gene promoter activity. Thus, MKP-1 controls the insulin expression by downregulating a JNK/c-jun pathway.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				L. O'Driscoll, P. Gammell, E. McKiernan, E. Ryan, P. B. Jeppesen, S. Rani, and M. Clynes Phenotypic and global gene expression profile changes between low passage and high passage MIN-6 cells J. Endocrinol., December 1, 2006; 191(3): 665 - 676. [Abstract] [Full Text] [PDF]

				Y. Fujinaka, D. Sipula, A. Garcia-Ocana, and R. C. Vasavada Characterization of Mice Doubly Transgenic for Parathyroid Hormone-Related Protein and Murine Placental Lactogen: A Novel Role for Placental Lactogen in Pancreatic {beta}-Cell Survival Diabetes, December 1, 2004; 53(12): 3120 - 3130. [Abstract] [Full Text] [PDF]

				M. Homme, C. P. Schmitt, O. Mehls, and F. Schaefer Mechanisms of Mitogen-Activated Protein Kinase Inhibition by Parathyroid Hormone in Osteoblast-Like Cells J. Am. Soc. Nephrol., November 1, 2004; 15(11): 2844 - 2850. [Abstract] [Full Text] [PDF]

				R. Aikin, D. Maysinger, and L. Rosenberg Cross-Talk between Phosphatidylinositol 3-Kinase/AKT and c-Jun NH2-Terminal Kinase Mediates Survival of Isolated Human Islets Endocrinology, October 1, 2004; 145(10): 4522 - 4531. [Abstract] [Full Text] [PDF]