p75, a member of the heat shock protein family, undergoes tyrosine phosphorylation in response to oxidative stress.
The combination of H2O2 and vanadate generates aqueous peroxovanadium (pV) species, which are effective cell-permeable oxidants, and potent inhibitors of protein-tyrosine phosphatases. As a result, treatment of intact cells with pV compounds significantly enhances protein Tyr phosphorylation. Here we demonstrate that treatment of intact rat hepatoma Fao cells with pV markedly enhances Tyr phosphorylation of a 75-kDa protein, termed pp75. Amino-terminal sequencing of pp75 revealed that this protein is a member of the 70-75-kDa heat shock protein family, which includes PBP-74, glucose-related protein (GRP)-75, and mortalin. Tyr phosphorylation of pp75 is selective, because other proteins that belong to the heat shock protein 70 family, such as GRP-72, Bip (GRP-78), and HSC-70 fail to undergo Tyr phosphorylation when cells are treated with pV. Our findings suggest that heat shock proteins such as pp75 may undergo tyrosine phosphorylation when intact cells are subjected to oxidative stress induced by pV compounds.
Hadari
Y R
YR
Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot, Israel.
Haring
H U
HU
Zick
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D002451:Cell Compartmentation; D002478:Cells, Cultured; D015180:Electrophoresis, Gel, Two-Dimensional; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins; D008099:Liver / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010750:Phosphoproteins / Q000378:metabolism*; D019000:Phosphotyrosine / Q000378:metabolism*; D051381:Rats; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; C526296:Irs1 protein, rat; D010750:Phosphoproteins; C103863:pp75 protein, rat; D019000:Phosphotyrosine