SHP2 binds catalase and acquires a hydrogen peroxide-resistant phosphatase activity via integrin-signaling.
Here, we examined whether catalase binds SHP2 and alters SHP2 susceptibility to H2O2. Our results indicated that serum and fibrinogen commonly evoked catalase binding to SHP2 in HeLa and A549 cells in a herbimycin-A and TNFalpha sensitive manner. Expression of active catalase nearly 15-fold over control levels in tet-off HeLa cells substantially increased the SHP2 binding, and the catalase-associated SHP2 displayed significantly high phosphatase activities with a H2O2-resistance compared to those with little catalase. Site-directed mutagenesis at 280 abolished the binding capability of catalase to SHP2-SH2 in vitro. These results suggest that catalase-280pYIQV binds SHP2 via integrin-signaling to increase a H2O2-resistant SHP2 activity.
Yano
Sumio
S
Department of Biochemistry, Ponce School of Medicine, Ponce, PR 00731, USA. yanos@coqui.net
Arroyo
Nelly
N
Yano
Noriko
N
D016227:Benzoquinones; D001665:Binding Sites; D002374:Catalase / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D016895:Culture Media, Serum-Free; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004912:Erythrocytes / Q000378:metabolism; D005340:Fibrinogen / Q000494:pharmacology; D005982:Glutathione Transferase / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D016023:Integrins / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D007700:Kinetics; D047029:Lactams, Macrocyclic; D008024:Ligands; D008954:Models, Biological; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D011233:Precipitin Tests; D011485:Protein Binding; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D011809:Quinones / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017828:Rifabutin / Q000031:analogs & derivatives; D044967:Serum / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016227:Benzoquinones; D016895:Culture Media, Serum-Free; D004791:Enzyme Inhibitors; D016023:Integrins; D047908:Intracellular Signaling Peptides and Proteins; D047029:Lactams, Macrocyclic; D008024:Ligands; D011809:Quinones; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; D017828:Rifabutin; C020754:herbimycin; D005340:Fibrinogen; D006861:Hydrogen Peroxide; D002374:Catalase; D005982:Glutathione Transferase; D010744:Phosphoric Monoester Hydrolases; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases