Regulation of insulin receptor signaling by the protein tyrosine phosphatase TCPTP

Galic, S., Klingler-Hoffmann, M., Fodero-Tavoletti, M. T., Puryer, M. A., Meng, T. C., Tonks, N. K., Tiganis, T. (March 2003) Regulation of insulin receptor signaling by the protein tyrosine phosphatase TCPTP. Molecular and Cellular Biology, 23 (6). pp. 2096-2108. ISSN 0270-7306

URL: http://www.ncbi.nlm.nih.gov/pubmed/12612081
DOI: 10.1128/​MCB.23.6.2096-2108.2003

Abstract

The human protein tyrosine phosphatase TCPTP exists as two forms: an endoplasmic reticulum-targeted 48-kDa form (TC48) and a nuclear 45-kDa form (TC45). Although targeted to the nucleus, TC45 can exit in response to specific stimuli to dephosphorylate cytoplasmic substrates. In this study, we investigated the downregulation of insulin receptor (IR) signaling by TCPTP. In response to insulin stimulation, the TC48-D182A and TC45-D182A "substrate-trapping" mutants formed stable complexes with the endogenous tyrosine-phosphorylated IR beta-subunit in 293 cells. Moreover, in response to insulin stimulation, the TC45-D182A mutant accumulated in the cytoplasm of cells overexpressing the IR and in part colocalized with the IR beta-subunit at the cell periphery. These results indicate that the IR may serve as a cellular substrate for both TC48 and TC45. In immortalized TCPTP-/- murine embryo fibroblasts, insulin-induced IR P-subunit tyrosine phosphorylation and protein kinase PKB/Akt activation were enhanced relative to the values in TCPTP+/+ cells. Importantly, the expression of TC45 or TC48 to physiological levels suppressed the enhanced insulin-induced signaling in TCPTP-/- cells. These results indicate that the differentially localized variants of TCPTP may dephosphorylate the IR and downregulate insulin-induced signaling in vivo.

Item Type: Paper
Uncontrolled Keywords: GROWTH-FACTOR RECEPTOR SUBSTRATE-TRAPPING MUTANTS MICE LACKING NEGATIVE REGULATOR HEPATOMA-CELLS HUMAN-PLACENTA B ACTIVATION PTP-PEST IN-VIVO TC-PTP
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types
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: Matt Covey
Date: March 2003
Date Deposited: 01 Jul 2013 16:40
Last Modified: 01 Jul 2013 16:40
PMCID: PMC149470
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27893

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