Calpain-mediated degradation of reversibly oxidized protein-tyrosine phosphatase 1B.
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.
Trümpler
Antje
A
Institute of Molecular Cell Biology, Friedrich Schiller University, Jena, Germany.
Schlott
Bernhard
B
Herrlich
Peter
P
Greer
Peter A
PA
Böhmer
Frank-D
FD
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002154:Calpain / Q000378:metabolism*; D020134:Catalytic Domain; D003545:Cysteine / Q000737:chemistry; D017931:DNA Primers / Q000235:genetics; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010084:Oxidation-Reduction; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction
D017931:DNA Primers; D007328:Insulin; D011994:Recombinant Proteins; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D017027:Protein Tyrosine Phosphatases; D002154:Calpain; D003545:Cysteine