J. Cancer Mol. 2: 9-16, 2006

[Review Article] 

Cys-Oxidation of Protein Tyrosine Phosphatases: Its Role in Regulation of Signal Transduction and Its Involvement in Human Cancers

Tzu-Ching Meng, Yi-Wei Lou, Yi-Yun Chen, Shu-Fang Hsu, and Yi-Fen Huang

Institute of Biological Chemistry, Academia Sinica and Institute of Biochemical Sciences, College of Life Sciences, National Taiwan University, Taipei, Taiwan [T.-C. Meng, Y.-W. Lo, S.-F. Hsu, Y.-F. Huang]; National Core Facility for Proteomics Research, Academia Sinica, Taipei, Taiwan [Y.-Y. Chen]

Abstract:

Reactive oxygen species (ROS) are currently viewed as secondary messengers that control signal transduction through the post-translational modifications of Cys-oxidation in targeting proteins.  The physiological levels of ROS are generated in response to stimulation induced by extracellular ligands.  Due to the labile feature of ROS, the effect of protein oxidation is normally transient.  Such a character is essential for the precise control of redox-dependent signaling homeostasis.  Nevertheless, studies have shown that under pathological conditions, such as certain types of cancer, the cellular ROS are produced in a ligand-independent manner.  Interestingly, the generation of ROS is required for the development of transformed phenotype and tumors, suggesting that the constitutive oxidation of signaling modulators might contribute to the uncontrolled signaling cascades, further leading to pathological consequences.  Emerging evidence has revealed that protein tyrosine phosphatases (PTPs), which regulate tyrosine phosphorylation-dependent signal transduction through tyrosine dephosphorylation of substrates, are highly susceptible to oxidation.  Interestingly, oxidation of catalytic Cys residue results in enzymatically inactivated form of PTPs, concomitant with an enhanced tyrosine phosphorylation level in cells.  The primary focus of this review is to comprehend recent studies that greatly advanced our understanding towards redox-dependent regulation of cell signaling through Cys oxidation of endogenous PTPs.  The rational implication of this mechanism in contributing to the development and maintenance of cell transformation is discussed.   

Received 11/9/05; Revised 2/3/06; Accepted 2/4/06.

¹Correspondence: Dr. Tzu-Ching Meng, Institute of Biological Chemistry, Academia Sinica, 128 Academia Road Sec. 2, Taipei 115, Taiwan. Phone: 886-2-27855696. Fax: 886-2-27892161. Email: tcmeng@gate.sinica.edu.tw

²Abbreviations: ROS, reactive oxygen species; Nox, NADPH oxidase; PI3-K, phosphatidylinositol 3-kinase; PTP, protein tyrosine phosphatase; PTK, protein tyrosine kinase; DUSP, dual specificity phosphatase; MKP, MAP kinase phosphatase.