Suppression of the phosphorylation of receptor tyrosine phosphatase-alpha on the Src-independent site tyrosine 789 by reactive oxygen species.
Oxidation of receptor protein tyrosine phosphatase-alpha (RPTPalpha) is emerging as an important yet poorly characterized regulatory mechanism for RPTPalpha signaling in cells. RPTPalpha has been shown to be reversibly oxidized and inhibited by reactive oxygen species. However, it is not known whether oxidative stress could regulate the phosphorylation of Tyr789, a critical tyrosine residue for RPTPalpha signaling that modulates the function of Grb2 and the activation of Src family kinases. In the present study, we have taken advantage of a phosphospecific antibody against Tyr789-phosphorylated RPTPalpha and characterized the phosphorylation of RPTPalpha Tyr789 in various cultured cells, including SYF cells lacking all three ubiquitously expressed members (Src, Yes, and Fyn) of Src family kinases. We have obtained substantial evidence indicating that the phosphorylation of RPTPalpha Tyr789 is regulated predominantly by an Src kinase inhibitor, protein phosphatase 1 (PP1)-sensitive but Src/Yes/Fyn-independent tyrosine kinase, in cells. We further reported a novel finding that, besides the inhibition of RPTPalpha's activity, H(2)O(2) at low to moderate concentrations (50-250 microM) markedly suppressed the phosphorylation of RPTPalpha Tyr789 and the association of RPTPalpha with Grb2 in cultured cells, which may result from inhibition of such a PP1-sensitive but Src/Yes/Fyn-independent tyrosine kinase. Because Tyr789 plays an important role in RPTPalpha signaling, our findings may provide new insights into the functional regulation of RPTPalpha by oxidative stress in cells.
Hao
Qin
Q
Department of Biochemistry, The University of Texas Health Center at Tyler, 11937 US Highway 271, Tyler, TX 75708, USA.
Rutherford
Stacey A
SA
Low
Brad
B
Tang
Hua
H
D002478:Cells, Cultured; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors*; D014443:Tyrosine / Q000378:metabolism*; D014867:Water / Q000494:pharmacology*; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism*
D017382:Reactive Oxygen Species; D011956:Receptors, Cell Surface; D014867:Water; D014443:Tyrosine; D019061:src-Family Kinases; D054645:Protein Phosphatase 1; C516841:PTPRA protein, human; D017027:Protein Tyrosine Phosphatases; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4