title: Inhibition of PTPs by H(2)O(2) regulates the activation of distinct MAPK pathways.
abstract: It has been shown that endogenous production of reactive oxygen species (ROS) during T cell activation regulates signaling events including MAPK activation. Protein tyrosine phosphatases (PTPs) have been regarded as targets of ROS which modify the catalytic cysteine residues of the enzymes. We have analyzed the interplay between the inhibition of PTPs and the activation of MAPK by H(2)O(2). Stimulation of Jurkat T cells with H(2)O(2) induces the phosphorylation of ERK, p38, and JNK members of MAPK family. H(2)O(2) stimulation of T cells was found to inhibit the PTP activity of CD45, SHP-1, and HePTP. Transfection of cells with wtSHP-1 decreased H(2)O(2)-induced ERK and JNK phosphorylation without affecting p38 phosphorylation. Transfection with wtHePTP inhibited H(2)O(2)-induced ERK and p38 phosphorylation without inhibiting JNK phosphorylation. The Src-family kinase inhibitor, PP2, inhibited the H(2)O(2)-induced phosphorylation of ERK, p38, and JNK. The phospholipase C (PLC) inhibitor, U73122, or the protein kinase C (PKC) inhibitor, Ro-31-8425, blocked H(2)O(2)-induced ERK phosphorylation, whereas the same treatment did not inhibit p38 or JNK phosphorylation. Taken together, these results suggest that inhibition of PTPs by H(2)O(2) contributes to the induction of distinct MAPK activation profiles via differential signaling pathways.
authors.affiliation: Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Kyoungmun
authors.initials: K
authors.lastname: Lee
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Esselman
mesh_terms: D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004963:Estrenes / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D019169:Jurkat Cells / Q000187:drug effects / Q000201:enzymology; D017493:Leukocyte Common Antigens / Q000502:physiology; D008213:Lymphocyte Activation; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008301:Maleimides / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D054558:Protein Tyrosine Phosphatases, Non-Receptor; D011743:Pyrimidines / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000502:physiology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000201:enzymology; D014162:Transfection; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000502:physiology
chemical_list: C412373:AG 1879; D004791:Enzyme Inhibitors; D004963:Estrenes; D007211:Indoles; D047908:Intracellular Signaling Peptides and Proteins; D008301:Maleimides; D009363:Neoplasm Proteins; D011743:Pyrimidines; D011760:Pyrrolidinones; D017382:Reactive Oxygen Species; D011993:Recombinant Fusion Proteins; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C071924:Ro 31-8425; D006861:Hydrogen Peroxide; D019061:src-Family Kinases; D011493:Protein Kinase C; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D017493:Leukocyte Common Antigens; C509249:PTPN6 protein, human; C502159:PTPN7 protein, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; D054558:Protein Tyrosine Phosphatases, Non-Receptor; D010738:Type C Phospholipases