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Updated: Aug 20, 2026

Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors
Published on: July 17, 2020
SHP2 binds catalase and acquires a hydrogen peroxide-resistant phosphatase activity via integrin-signaling
Sumio Yano1, Nelly Arroyo, Noriko Yano
1Department of Biochemistry, Ponce School of Medicine, Ponce, PR 00731, USA. yanos@coqui.net
Abstract:
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.
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