Gongqin Sun

Professor and Department Chair
Office: 389 CBLS Building
Telephone: (401) 874-5937
Email: gsun@uri.edu

Education
  • Ph. D., University of Nebraska-Lincoln, 1992
 
Research Areas

Cells go through different genetically programmed processes, such as growth, division, differentiation and death in response to specific signals that may be external (such as exposure to hormones) or internal signals (such as result from DNA damage). Signal transduction is the process that communicates such signals to specific protein targets (including enzymes) that perform critical functions in the cell. The most common mechanism of signal transduction involves protein phosphorylation, wherein a phosphate from ATP is transferred to a serine, threonine or tyrosine residue in a target protein. Protein phosphorylation often serves as a switch to turn "on" or "off" the activity of a protein. Enzymes that catalyze protein phosphorylation reactions are called protein kinases. Depending on the residue they phosphorylate, protein kinases are classified into protein serine/threonine kinases and protein tyrosine kinases. Constitutive activation of protein tyrosine kinases often results in cell growth and division in the absence of an external growth signal, transforming a normal cell into a cancer cell. For this reason, many protein tyrosine kinases are targets for anticancer drug discovery. There are more than 100 different protein tyrosine kinases in the cell. They all catalyze the same chemical reaction, but recognize different target proteins and respond to different regulatory signals. These differences enable them to perform different specific functions in the cell. We are interested in understanding the structure-function and structure-regulation relationships and hope to apply such understanding to develop novel strategies to block their function. Such research is carried out with a few cytosolic protein tyrosine kinases, such as Csk and Src as model systems. Our approaches include gene cloning, protein expression and purification, site-specific mutagenesis, enzyme kinetics, spectroscopy, and small molecule and peptide inhibitors.

 
Selected Publications
  • Sun, G., Sharma, A. K. and Budde, R. J. A. Autophosphorylation of Src and Yes blocks their inactivation by Csk phosphorylation. Oncogene 15, 1587-1595, 1998.
  • Sun, G., Ramdas, L., Wang, W., Vinci, J., McMurray, J., and Budde, R. J. A. Effect of autophosphorylation on the catalytic and regulatory properties of Src. Archiv. Biochem. Biophys. 397, 11-17, 2002.
  • Shaffer J., Sun G., and Adams J. A. Nucleotide release and associated conformational changes regulate function in the COOH-terminal src kinase, csk. Biochemistry 40, 11149-11155, 2001.
  • Sun, G., and Budde, R. J. A. Affinity purification of Csk protein tyrosine kinase based on its catalytic requirement for divalent metal cations. Protein Exp. Purif., 21, 8-12, 2001.
  • Budde, R. J. A., Ramdas, L., Sun, G. Cloning, expression, purification and characterization of the alternate splice Src variants for drug discovery. J. Mol. Catalysis, 11, 805-809, 2001.
  • Wang, W., Ramdas, L., Sun, G., Ke, S., Obeyesekere, N. U., Budde, R. J. A. and McMurray, J. S. Cyclic peptides incorporating 4-carboxyphenylalanine and phosphotyrosine are potent inhibitors of the kinase activity pp60c-src. Biochemistry, 39, 5221-5228, 2000.
  • Sun, G., and Budde, R. J. A. Mutations in the N-terminal regulatory region reduce the catalytic activity of Csk, but do not affect its recognition of Src. Archiv. Biochem. Biophys. 367, 167-172, 1999.
  • Ramdas, L., Bunnin, B. A., Plunkett, M. J., Sun, G., Ellman, J., Gallick, G. and Budde, R. J. A. Benzodiazepine compounds as inhibitors of the Src protein tyrosine kinase: screening of a combinatorial library of 1,4-benzodiazepines. Archiv. Biochem. Biophys. 368, 394-400, 1999.
  • Sun, G., Bailey, D., Jones, M. W., and Markwell, J. Chloroplast thylakoid protein phosphatase is a membrane surface-associated activity. Plant Physiol. 89, 238-243, 1989.
  • Ramdas, L., Obeyeskere, N. U., Sun, G., McMurray, J. S. and Budde, R. J. A. N-Myristoylation of a peptide substrate for Src converts it into an apparent slow-binding bisubstrate-type inhibitor. J. Peptide Res. 53, 569-577, 1999.
  • Lin, X., Lee, S., and Sun, G. Functions of the Activation Loop in Csk Protein Tyrosine Kinase. J. Biol. Chem. 278, 24072-24077, 2003.
  • Sun, G., and Budde, R. J. A. Expression, purification and initial characterization of human Yes protein tyrosine kinase from a bacterial expression system. Archiv. Biochem. Biophys. 345, 135-142, 1997.
  • Sun, G., Ke, S. and Budde, R. J. A. Csk phosphorylation and inactivation in vitro by the cAMP-dependent protein kinase. Archiv. Biochem. Biophys. 343, 194-200, 1997.
  • Sun, G., and Budde, R. J. A. Requirement for an additional divalent metal cation to activate protein tyrosine kinases. Biochemistry 36, 2139-2146, 1997.
  • Sun, G., and Budde, R. J. A. A modified pGEX expression system that eliminates degradation products and thrombin from the recombinant protein. Analyt. Biochem. 231, 458-460, 1995.
  • Li, S., Sun, G., and Budde, R. J. A.. Production and characterization of monoclonal antibodies against the recombinant Csk protein tyrosine kinase: a tool for signal transduction research. Hybridoma 14, 341-346, 1995.
  • Sun, G., Sarath, G., and Markwell, J. Phosphopeptides as substrates for thylakoid protein phosphatase activity. Arch Biochem. Biophys. 304, 490-495, 1993.
  • Sun, G., and Markwell, J. Lack of types 1 and 2A protein serine(P)/threonine(P) phosphatase activities in chloroplasts. Plant Physiol. 100, 620-624, 1992.
  • Markwell, J., Sun, G., and Jones, M. W. Chloroplast protein phosphatase from wheat. Current Top. Plant Biochem. Physiol. 9, 282-291, 1990.
  • Sun, G., and Budde, R. J. A. Substitution studies of the second divalent metal cation requirement of protein tyrosine kinase Csk. Biochemistry 38, 5659-5665, 1999.
  • Parang K, and Sun G. Protein Kinase Inhibitors in Drug Discovery. in Drug Discovery Handbook, Gad S. ed., John Wiley & Sons, Inc., Hoboken, New Jersey. pp1191-1257, 2005.
  • Kemble DJ, Wang YH, and Sun G. Bacterial expression and characterization of catalytic loop mutants of Src protein tyrosine kinase. Biochemistry, in press, 2006.
  • Ayrapetov MK, Wang Y, Lin X, Gu X, Parang K, and Sun G. Conformational basis of SH2-pTyr527 binding in Src inactivation. J. Biol. Chem. 281, 23776-23784, 2006.
  • Wang Y, Ayrapetov MK, Lin X, and Sun G. A new strategy to produce active human Src from bacteria for biochemical study of its regulation. Biochem. Biophys. Res. Comm. 346, 606-611, 2006.
  • Kumar A, Ye G, Wang Y, Lin X, Sun G, Parang K. Synthesis and Structure-Activity Relationships of Linear and Conformationally Constrained Peptide Analogs of CIYKYY as Src Tyrosine Kinase Inhibitors. J. Med. Chem. 49, 3395-3401, 2006.
  • Lin X, Wang Y, Ahmedeni Y, Parang K, and Sun G. Structural basis for domain-domain communication in a protein tyrosine kinase, the C-terminal Src kinase. J. Mol. Biol., 357, 1263-1273, 2006.
  • Lee S, Ayrapetov MK, Kemble DJ, Parang K, and Sun G. Docking-based substrate recognition by the catalytic domain of a protein tyrosine kinase, Csk. J. Biol. Chem. 281, 8183-8189, 2006.
  • Lin X, Ayrapetov M, and Sun G. Characterization of the interactions between the active site of a protein tyrosine kinase and a divalent metal activator. BMC Biochem, 6, 25, 2005.
  • Ye G, Ayrapetov M, Nam NH, Sun G, and Parang K. Solid-phase binding assays of peptides using EGFP-Src SH2 domain fusion protein and biotinylated Src SH domain. Bioorg. Med. Chem Lett. 15, 4994-4997, 2005.
  • Lee, S., Lin, X., McMurray, J., and Sun, G. Contribution of an active site cation-p interaction to the spectroscopic properties and catalytic function of protein tyrosine kinase Csk. Biochemistry 41, 12107-12114, 2002.
  • Ayrapetov MK, Nam NH, Parang K, and Sun G. Functional diversity of Csk, Chk and Src SH2 domains due to a single residue variation. J. Biol. Chem. 280, 25780-25787, 2005.
  • Ayrapetov, M. K., Lee, S., and Sun, G. Expression, Purification and Biochemical Characterization of Chk, a Soluble Protein Tyrosine Kinase. Protein Exp. Purif. 29, 148-155, 2003.
  • Lieser S, Marlow C, Aubol BE, Lee S, Sun G, and Adams JA. Phosphoryl transfer step in Csk controls Src recognition. J. Biol. Chem. 280, 7769-7776, 2005.
  • Lin X, Ayrapetov MK, Lee S, and Sun G. Probing the communication between the regulatory and catalytic domains of a protein tyrosine kinase, Csk. Biochemistry 44, 1561-1567, 2005.
  • Parang K, and Sun G. Design strategies for protein kinase inhibitors. Curr. Opin. Drug Discov. Devel. 7, 617-629, 2004.
  • Nam NH, Lee S, Ye G, Sun G, Parang K. ATP-phosphopeptide conjugates as inhibitors of Src tyrosine kinases. Bioorg. Med. Chem. 12, 5753-5766, 2004.
  • Nam NH, Ye G, Sun G, and Parang K. Conformationally constrained peptide analogues of pTyr-Glu-Glu-Ile as inhibitors of the Src SH2 domain binding. J. Med. Chem. 47, 3131-41, 2004.
  • Nam NH, Pitts R, Sun G, Sardari S, Tiemo A, Xie M, Yan B, and Parang K. Design of tetrapeptide ligands as inhibitors of the Src SH2 domain. Bioorg Med Chem. 12, 779-787, 2004.
  • Lee S, Lin X, Nam NH, Parang K, and Sun G. Determination of the Substrate-Docking Site of Protein Tyrosine Kinase Csk. Proc. Natl. Acad. Sci. U. S. A., 100, 14707-14712, 2003.
  • Gu X, Wang Y, Kumar A, Ye G, Parang K, and Sun G. Design and evaluation of phenylalanine and tyrosine hydroxamate derivatives as metal-mediated inhibitors of a protein tyrosine kinase. J. Med. Chem, in press, 2006
  • Parang K, and Sun G. Recent advances in the discovery of Src kinase inhibitors. Exp. Opin. Ther. Patents 15, 1183-1207, 2005.