TAILIEUCHUNG - Báo cáo khoa học: Calpain-mediated degradation of reversibly oxidized protein-tyrosine phosphatase 1B

Protein-tyrosine phosphatases (PTPs) are regulated by reversible inactivat-ing oxidation of the catalytic-site cysteine. We have previously shown that reversible oxidation upon UVA irradiation is followed by calpain-mediated PTP degradation. Here, we address the mechanism of regulated cleavage and the physiological function of PTP degradation. | Calpain-mediated degradation of reversibly oxidized protein-tyrosine phosphatase 1B Antje Trumpler1 Bernhard Schlott2 Peter Herrlich2 Peter A. Greer3 and Frank-D. Bohmer1 1 Institute of Molecular CellBiology Friedrich Schiller University Jena Germany 2 Leibniz Institute for Age Research - Fritz Lipmann Institute Jena Germany 3 Division of Cancer Biology and Genetics Queen s University Cancer Research Institute Kingston Canada Keywords calpain degradation insulin signaling oxidation protein-tyrosine phosphatase Correspondence . Bohmer Institute of Molecular Cell Biology Hans-Knoll-Strasse 2 D-07745 Jena Germany Fax 49 3641 939 5602 Tel 49 3641 939 5631 E-mail boehmer@ Received 20 January 2009 revised 22 July 2009 accepted 3 August 2009 doi Protein-tyrosine phosphatases PTPs are regulated by reversible inactivating oxidation of the catalytic-site cysteine. We have previously shown that reversible oxidation upon UVA irradiation is followed by calpain-mediated PTP degradation. Here we address the mechanism of regulated cleavage and the physiological function of PTP degradation. Reversible oxidation of PTP1B in vitro strongly facilitated the association with calpain and led to greatly increased calpain-dependent inactivating cleavage. Both oxidation-induced association and cleavage depended exclusively on the presence of the catalytic reversibly oxidized cysteine residue 215. A major cleavage site was identified preceding amino acid position Ala77. In calpain-deficient cells insulin signaling was apparently diminished consistent with a possible role for calpain in removing a negative regulator of insulin signaling. Reversibly oxidized PTP1B may be a target of calpain in this context. Structured digital abstract MINT-7234580 Calpain 4 uniprotkb P04632 and Calpain 1 uniprotkb P07384 physically interact MI 0915 with PTP1B uniprotkb P18031 by enzyme linked immunosorbent assay MI 0411 MINT-7234562 MINT-7234481 Calpain 4 .

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