Conclusion
The proposed role of H2O2 in growth factor signaling is depicted in Fig. 5. In the model, H2O2 induces reversible inactivation of PTPs and PTEN through oxidation of their essential Cys residues. This model suggests that the receptor-mediated activation of RTK and PI 3-kinase may not be sufficient for the accumulation of tyrosine phosphorylated proteins and 3′-phosphorylated PIs because of the opposing activity of PTPs and PTEN, respectively. The concomitant inactivation of PTPs and PTEN by H2O2 produced in response to receptor stimulation might also be necessary for these effects. This model is consistent with the previous observations that H2O2 generation and accumulation are necessary for downstream actions of PDGF and EGF that are mediated by RTK and PI 3-kinase. In the absence of the proposed function of H2O2 the activation of RTK and PI 3-kinase would result in futile cycles of phosphorylation / dephosphorylation of proteins and phosphoinositide.
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Rhee, S.G., Lee, SR., Yang, KS., Kwon, J., Kang, S.W. (2003). Hydrogen Peroxide as Intracellular Messenger: Identification of Protein Tyrosine Phosphatases and Pten as H2O2 Target. In: Forman, H.J., Fukuto, J., Torres, M. (eds) Signal Transduction by Reactive Oxygen and Nitrogen Species: Pathways and Chemical Principles. Springer, Dordrecht. https://doi.org/10.1007/0-306-48412-9_9
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