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) Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map 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 Cui, L. Articles by Pallen, C. J. Search for Related Content PubMed PubMed Citation Articles by Cui, L. Articles by Pallen, C. J. Social Bookmarking                      What's this?

J Biol Chem, Vol. 273, Issue 52, 34784-34791, December 25, 1998

Insulin Secretagogues Activate the Secretory Granule Receptor-like Protein-tyrosine Phosphatase IAR

From the Cell Regulation Laboratory, Institute of Molecular and Cell Biology, 30 Medical Drive, Singapore 117609, Republic of Singapore

To investigate the potential role of protein-tyrosine phosphatases (PTPs) in regulated secretion, cellular PTP activity was measured in pancreatic  cell lines after exposure to insulin secretagogues. A peak of elevated PTP activity was detected in whole cell lysates after 15-20 min of treatment of the cells with high KCl, glucose, or TPA, which did not appear upon treatment with control compounds. Neither was it detected in cells that do not undergo regulated secretion. The PTP activation was transient, SDS-resistant, and localized to the cytoskeleton fraction of cells. The cytoskeletal localization of IAR, a receptor-like PTP associated with secretory granules of neuroendocrine cells, suggested the possibility that IAR is the secretagogue-activated PTP. The transient expression of human IAR in TC3 and HIT-T15  cells, followed by treatment with secretagogues or control compounds and immunoprecipitation of human IAR, showed that immunoprecipitates from the secretagogue-treated cells contained an elevated PTP activity. The secretagogue-induced activation of IAR had identical kinetics to that of the endogenous PTP. Although ectopic IAR was present in membrane and cytoskeletal fractions from the cells, only the cytoskeleton-associated IAR could be activated. Thus IAR represents the endogenous secretagogue-responsive PTP, or at least a component of it, and is one of the few receptor-like PTPs for which enzymatic activation has been demonstrated. Insulin secretion is detected prior to IAR activation, suggesting that IAR is not required for immediate secretion but likely plays a role in events downstream of insulin secretion or in another pathway related to the specialized function of secretory cells.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				S. Gross, C. Blanchetot, J. Schepens, S. Albet, R. Lammers, J. den Hertog, and W. Hendriks Multimerization of the Protein-tyrosine Phosphatase (PTP)-like Insulin-dependent Diabetes Mellitus Autoantigens IA-2 and IA-2beta with Receptor PTPs (RPTPs). INHIBITION OF RPTPalpha ENZYMATIC ACTIVITY J. Biol. Chem., December 6, 2002; 277(50): 48139 - 48145. [Abstract] [Full Text] [PDF]