Skip Navigation

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
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 Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Request Permissions
Google Scholar
Right arrow Articles by Shi, K.
Right arrow Articles by Kashiwagi, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shi, K.
Right arrow Articles by Kashiwagi, A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

J. Biochem, 2004, Vol. 136, No. 1 89-96
© 2004 The Japanese Biochemical Society

CELL

Protein-Tyrosine Phosphatase 1B Associates with Insulin Receptor and Negatively Regulates Insulin Signaling without Receptor Internalization

Kun Shi1, Katsuya Egawa1, Hiroshi Maegawa1,*, Takaaki Nakamura2, Satoshi Ugi1, Yoshihiko Nishio1 and Atsunori Kashiwagi2

1 Division of Endocrinology and Metabolism, Department of Medicine, and 2 Department of Anatomy, Shiga University of Medical Science, Otsu 520-2192

Phosphorylated platelet-derived growth factor (PDGF) receptor becomes internalized and then is dephosphorylated by protein-tyrosine phosphatase (PTP) 1B at the endoplasmic reticulum (ER). However, it remains unclear where PTP1B dephosphorylates insulin receptor and inhibits its activity. To clarify how and where PTP1B could interact with insulin receptor, we overexpressed a phosphatase-inactive mutant, PTP1BC/S, in 3T3-L1 adipocytes. Although PDGF receptor was maximally associated with PTP1BC/S at 30 min after PDGF stimulation, the maximal association of insulin receptor with PTP1BC/S was attained at 5 min after insulin stimulation. Furthermore, dansylcadaverine, a blocker of receptor internalization, inhibited this PDGF-induced association of PTP1BC/S with its receptor. However, dansylcadaverine did not affect the insulin-stimulated association of PTP1BC/S with insulin receptor, as well as dephosphorylation of insulin receptor by PTP1B. These results indicate that PTP1B might interact with insulin receptor and deactivate it without internalization. Finally, we overexpressed the wild-type and cytosolic-form of PTP1B to determine the role of ER-anchoring of PTP1B, and found that both inhibited insulin signaling equally. Thus, our data indicate that localization of PTP1B at the ER is not needed for insulin receptor dephosphorylation by PTP1B.

* To whom correspondence should be addressed. Tel: +81-77-548-2222, Fax: +81-77-543-3858, E-mail: maegawa{at}belle.shiga-med.ac.jp


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Lipid Res.Home page
R. MacLaren, W. Cui, S. Simard, and K. Cianflone
Influence of obesity and insulin sensitivity on insulin signaling genes in human omental and subcutaneous adipose tissue
J. Lipid Res., February 1, 2008; 49(2): 308 - 323.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. M. Picha, S. S. Patel, S. Mandiyan, J. Koehn, and L. P. Wennogle
The Role of the C-terminal Domain of Protein Tyrosine Phosphatase-1B in Phosphatase Activity and Substrate Binding
J. Biol. Chem., February 2, 2007; 282(5): 2911 - 2917.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
B. J. Goldstein, K. Mahadev, and X. Wu
Redox Paradox: Insulin Action Is Facilitated by Insulin-Stimulated Reactive Oxygen Species With Multiple Potential Signaling Targets
Diabetes, February 1, 2005; 54(2): 311 - 321.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.