Galic, S., Hauser, C., Kahn, B. B., Haj, F. G., Neel, B. G., Tonks, N. K., Tiganis, T. (January 2005) Coordinated regulation of insulin signaling by the protein tyrosine phosphatases PTP1B and TCPTP. Molecular and Cellular Biology, 25 (2). pp. 819-829. ISSN 0270-7306
Abstract
The protein tyrosine phosphatase PTP1B is a negative regulator of insulin signaling and a therapeutic target for type 2 diabetes. Our previous studies have shown that the closely related tyrosine phosphatase TCPTP might also contribute to the regulation of insulin receptor (IR) signaling in vivo (S. Galic. M. Klingler-Hoffmann, M. T. Fodero-Tavoletti, M. A. Puryer, T. C. Meng, N. K. Tonks. and T. Tiganis. Mol. Cell. Biol. 23:2096-2108, 2003). Here we show that PTP1B and TCPTP function in a coordinated and temporally distinct manner to achieve an overall regulation of IR phosphorylation and signaling. Whereas insulin-induced phosphatidylinositol 3-kinase/Akt signaling was prolonged in both TCPTP-/- and PTP1B(-/-) immortalized mouse embryo fibroblasts (MEFs), mitogen-activated protein kinase ERK1/2 signaling was elevated only in PTP1B-null MEFs. By using phosphorylation-specific antibodies, we demonstrate that both IR beta-subunit Y1162/Y1163 and Y972 phosphorylation are elevated in PTP1B(-/-) MEFs. whereas Y972 phosphorylation was elevated and Y1162/Y1163 phosphorylation was sustained in TCPTP-/- MEFs, indicating that PTP1B and TCPTP differentially contribute to the regulation of IR phosphorylation and signaling. Consistent with this. suppression of TCPTP protein levels by RNA interference in PTP1B(-/-) MEFs resulted in no change in ERK1/2 signaling but caused prolonged Akt activation and Y1162/Y1163 phosphorylation. These results demonstrate that PTP1B and TCPTP are not redundant in insulin signaling and that they act to control both common as well as distinct insulin signaling pathways in the same cell.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | growth factor recepter in-vivo adapter protein gene expression intact cells 1B mice resistance LAR dephosphorylation |
| Subjects: | diseases & disorders > nutritional and metabolic diseases > diabetes bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > protein tyrosine phosphatase |
| CSHL Authors: | |
| Communities: | CSHL labs > Tonks lab |
| Depositing User: | CSHL Librarian |
| Date: | January 2005 |
| Date Deposited: | 12 Jan 2012 21:46 |
| Last Modified: | 21 Feb 2017 20:50 |
| PMCID: | PMC543412 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/22573 |
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