Details

Autor(en) / Beteiligte

• Maas, Matthias
• Wang, Ronggang
• Paddock, Cathy
• Kotamraju, Srigiridhar
• Kalyanaraman, Balaraman
• Newman, Peter J
• Newman, Debra K

Titel

Reactive oxygen species induce reversible PECAM-1 tyrosine phosphorylation and SHP-2 binding

Ist Teil von

• American journal of physiology. Heart and circulatory physiology, 2003-12, Vol.285 (6), p.H2336-H2344

Ort / Verlag

United States

Erscheinungsjahr

2003

Quelle

MEDLINE

Beschreibungen/Notizen

• 1 Blood Research Institute, The Blood Center of Southeastern Wisconsin, 2 Department of Biophysics, 3 Cardiovascular Center, and Departments of 4 Cell Biology, 5 Pharmacology, and 6 Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226 Submitted 2 June 2003 ; accepted in final form 25 July 2003 Platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31) functions to control the activation and survival of the cells on which it is expressed. Many of the regulatory functions of PECAM-1 are dependent on its tyrosine phosphorylation and subsequent recruitment of the Src homology (SH2) domain containing protein tyrosine phosphatase SHP-2. The recent demonstration that PECAM-1 tyrosine phosphorylation occurs in cells exposed to the reactive oxygen species hydrogen peroxide (H 2 O 2 ) suggested that this form of oxidative stress may also support PECAM-1/SHP-2 complex formation. In the present study, we show that PECAM-1 tyrosine phosphorylation in response to exposure of cells to H 2 O 2 is reversible, involves a shift in the balance between kinase and phosphatase activities, and supports binding of SHP-2 and recruitment of this phosphatase to cell-cell borders. We speculate, however, that the unique ability of H 2 O 2 to reversibly oxidize the reactive site cysteine residues of protein tyrosine phosphatases may result in transient inactivation of the SHP-2 that is bound to PECAM-1 under these conditions. Finally, we provide evidence that PECAM-1 tyrosine phosphorylation and SHP-2 binding in endothelial cells requires exposure to an "oxidative burst" of H 2 O 2 , but that exposure of these cells to sufficiently high concentrations of H 2 O 2 for a sufficiently long period of time abrogates binding of SHP-2 to tyrosine-phosphorylated PECAM-1. These findings support a role for PECAM-1 as a sensor of oxidative stress, perhaps most importantly during the process of inflammation. phosphotyrosine; hydrogen peroxide; SHP-2; CD31 Address for reprint requests and other correspondence: D. K. Newman, Blood Research Institute, The Blood Center of Southeastern Wisconsin, PO Box 2178, Milwaukee, WI 53201-2178 (E-mail: dknewman{at}bcsew.edu ).