Identification of YB-1 as a regulator of PTP1B expression: implications for regulation of insulin and cytokine signaling

Fukada, T., Tonks, N. K. (February 2003) Identification of YB-1 as a regulator of PTP1B expression: implications for regulation of insulin and cytokine signaling. Embo Journal, 22 (3). pp. 479-493. ISSN 0261-4189

URL: http://www.ncbi.nlm.nih.gov/pubmed/12554649
DOI: 10.1093/emboj/cdg067

Abstract

Changes in expression of PTP1B, the prototypic protein tyrosine phosphatase, have been associated with various human diseases; however, the mechanisms by which PTP1B expression is regulated have not been defined. We have identified an enhancer sequence within the PTP1B promoter which serves as a binding site for the transcription factor Y box-binding protein-1 (YB-1). Overexpression of YB-1 resulted in increased levels of PTP1B. Furthermore, depletion of YB-1 protein, by expression of a specific antisense construct, led to an similar to70% decrease in expression of PTP1B, but no change in the level of its closest relative, TC-PTP. Expression of antisense YB-1 resulted in increased sensitivity to insulin and enhanced signaling through the cytokine receptor gp130, which was suppressed by re-expression of PTP1B. Finally, we observed a correlation between the expression of PTP1B and that of YB-1 in cancer cell lines and an animal model of type II diabetes. Our data reveal an important role for YB-1 as a regulator of PTP1B expression, and further highlight PTP1B as a critical regulator of insulin- and cytokine-mediated signal transduction.

Item Type: Paper
Uncontrolled Keywords: cytokine insulin phosphorylation PTP1B YB-1 PROTEIN-TYROSINE-PHOSPHATASE BOX-BINDING-PROTEIN EPIDERMAL GROWTH-FACTOR HUMAN BREAST-CANCER 1B IN-VIVO Y-BOX TRANSCRIPTION FACTORS CELL-PROLIFERATION TERMINAL SEQUENCE GENE-EXPRESSION
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing
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: February 2003
Date Deposited: 01 Jul 2013 19:56
Last Modified: 01 Jul 2013 19:56
PMCID: PMC140751
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27878

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