Phosphatases, phosphotyrosine PTPases

Intracellular and extracellular ROS activate tyrosine and serine-threonine kinases (i.e., the MAPK family members). Following TNF-a, TGF-f5 or EGF stimulation, intracellular ROS are generated which stimulate various signaling pathways [73], Tyrosine kinase receptors (e.g., EGF, PDGF and TGF-a) may be activated by ROS directly via protein sulfhydryl group modifications, or inhibition of phosphotyrosine phosphatases (PTPases) and subsequent receptor activation. The latter is possible as PTPases contain a redox-sensitive cysteine at their active site [78], and oxidation of protein sulfhydryl groups results in the inactivation of PTPases. 

PTEN, phosphatase and tensin homolog PTPase, phosphotyrosine phosphatase PYY, peptide YY... 

The PTPases share the signature motif (H/V)C(X)5R(S/T). This motif is also found in the low-molecular-weight PTPases, as well as in the VH 1-like dual-specific phosphatases, so-called because they dephosphorylate phosphotyrosine as well as phospho-Ser/Thr residues.129,149 These three groups of phosphatases have little sequence similarity other than the signature motif and the placement of the essential Cys and Arg residues in the active site. 

PTPase Phosphotyrosine phosphatase/protein tyrosine phosphatase ROS Reactive oxygen species... 

Figure 1 Insulin signal transduction cascade (simplified). Intracellular kinases affected by tyrosine phosphorylation activation/deactivation under phosphotyrosine phosphatase (PTPase) regulation (vanadium-inhibitable) include (especially) IRS-I, IRS-2, she, and MAPK. V indicates possible sites of vanadium s mechanism of action. Cytosolic protein tyrosine kinase (CytPTK, not shown) stimulation by phosphatase inhibition is independent of the insulin cascade, but is also multi-step, and is particularly susceptible to vanadyl stimulation...

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