The Protein Tyrosine Phosphatase (PTP) family comprises a large and diverse 
group of enzymes, regulating a range of biological processes through 
de-phosphorylation of many proteins and lipids. These enzymes share a catalytic 
mechanism that requires a reduced and reactive cysteine nucleophile, making them 
potentially sensitive to inactivation and regulation by oxidation. Analysis of 
ten PTPs identified substantial differences in the sensitivity of these enzymes 
to oxidation in vitro. More detailed experiments confirmed the following rank 
order of sensitivity: PTEN and Sac1>PTPL1/FAP-1>>myotubularins. When the 
apparent sensitivity to oxidation of these PTPs in cells treated with hydrogen 
peroxide was analysed, this correlated well with the observed sensitivities to 
oxidation in vitro. These data suggested that different PTPs may fall into at 
least three different classes with respect to mechanisms of cellular redox 
regulation. 1. PTEN and Sac1 were readily and reversibly oxidised in vitro and 
in cells treated with hydrogen peroxide 2. PTPL1 appeared to be resistant to 
oxidation in cells, correlating with its sensitivity to reduction by glutathione 
in vitro 3. The myotubularin family of lipid phosphatases was almost completely 
resistant to oxidation in vitro and in cells. Our results show that sensitivity 
to reversible oxidation is not a necessary characteristic of the PTPs and imply 
that such sensitivity has evolved as a regulatory mechanism for some of this 
large family, but not others.