Research in my lab focuses on the structure and function study of signaling molecules, with an emphasis on protein tyrosine phosphatases and protein-lipid interactions, by using enzymology, molecular biology, cellular biology X-ray crystallographic and antibody microarray techniques.
The first project is to understand the substrate specificity and regulatory mechanism of cytosolic protein tyrosine phosphatases called SHPs. SHPs are important proteins involved in receptor-mediated signal transduction pathway and are unique molecules endowed with multiple functions and subject to many levels of regulations in biological system. We want to determine their structures, both with and without the regulatory domains, and with different bound-ligands. In addition, SHP-1, one member of this family of proteins, has been demonstrated as a tumor suppressor gene. We intend to understand its tumor suppressing function on different cell lines and to develop a novel therapeutic method for the cancer treatment in the future.
The second project is to determine the structure and function of a phosphoinositide binding domain called PX (Phox) domain. The PX domain has recently been identified as a domain binding phosphoinositol phosphates (PIPs). Our goal is to determine the structure of different PX domains with different PIPs ligands and to understand the structural basis for the protein-lipid interactions. In addition, we want to understand the biological function of the PX domain containing proteins, such as p40, p47 in NADPH oxidase, and HS1BP3.
Antibody microarray is a novel technique for protein expression profile analysis. We shall use this technique to identify the novel biomarkers for the diagnosis of different cancer diseases.
Yang, J., Liu, L., He, D., Song, X., Liang, X., Zhao, Z. and Zhou, G. W. (2003). “Crystal Structure of Human protein tyrosine phosphatase SHP-1” J. Biol. Chem. 278, 6516-6520.
Wu, C., Sun, M., Liu, L. and Zhou, G. W. (2003) “The function of protein tyrosine phosphatase SHP-1 in cancer.” Gene. 306, 1-12. (Review).
Zhan, Y., Virbasius, J. V., Song, X., Pomerleau, D. P., Czech, M. P and Zhou, G. W. (2002) “p40phox PX domain and p47phox PX domain of NADPH oxidase target to membrane via direct and indirect recruitment by phosphoinositides” J. Biol. Chem.. 277, 4512-4518.
Virbasius, J. V., Song, X., Pomerleau, D. P., Zhan, Y., Zhou, G. W. and Czech, M. P. (2001) “Activation of the Akt-related cytokine-independent survival kinase requires interaction of its phox domain with endosomal phosphatidylinositol 3-phosphate.” Proc. Nat. Acad. Sci. 98, 12908-12913.
Song, X., Xu, W., Zhang, A., Huang, G., Liang, X., Virbasius, J. V., Czech, M. P., and Zhou, G. W. (2001) “Phox Homology (PX) Domains Specifically Bind Phosphatidylinositol Phosphates” Biochem. 40, 8940-8944.
Yang, J., Chen, Z., Niu, T., Liang, X., Zhao, Z. and Zhou, G. W. (2000). “Structural basis for Substrate Specificity of Protein Tyrosine Phosphatase SHP-1” J. Biol. Chem. 275, 4066-4071.