Division of Life Science
 
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Yung Hou WONG
PhD Cambridge
Chair Professor
Associate Dean of School of Science
Director of Biotechnology Research Institute
Co-Director of Molecular Neuroscience Center

Email: boyung@ust.hk

 
Research Interests
Prof. Wong’s major interests are currently focused on the delineation of the mechanisms of cell signaling, particularly those involving the G protein-coupled receptors (GPCRs). The functional capabilities of GPCRs that bind opioid peptides, melatonin, or chemokines, and their G protein-coupling specificities are examined in heterologous expression systems. Delineation of interacting domains on the GPCRs and their associated G proteins is achieved by the construction of chimeric and mutant signaling molecules. Detailed analysis of critical regions/residues responsible for providing the specificity of receptor-G protein interactions provides a framework for understanding the fidelity of cell signaling and the creation of novel tools for drug discovery. Signal integration at the level of effectors such as adenylyl cyclase, phospholipase C, and mitogen-activated protein kinases are examined in cultured mammalian cells. In addition, the roles of GPCRs and G proteins in the regulation of cell proliferation, differentiation, and the development of drug tolerance are examined using a variety of immunological, biochemical, pharmacological, and molecular biology techniques.

Representative Publications

  1. New DC, Wu KKH, Kwok AWS, and Wong YH (2007) G protein-coupled receptor-induced Akt activity in cellular proliferation and apoptosis. FEBS J. (in press).
     
  2. Chan ASL, Ng LWC, Poon LSW, Chan WWY and Wong YH (2007) dopaminergic and adrenergic toxicities on SK-N-MC human neuroblastoma cells are mediated through G protein signaling and oxidative stress. Apoptosis 12: 167-179.
     
  3. Liu AMF, Lo RKH, Wong CSS, Morris C, Wise H, and Wong YH (2006) Activation of STAT3 by Gas distinctively requires protein kinase A, JNK, and phosphatidylinositol 3-kinase. J. Biol. Chem. 281: 35812-35825.
     
  4. New DC, An H, Ip NY, and Wong YH (2006) GABAB heterodimeric receoptors promote Ca2+ influx via store-operated channels in rat cortical neurons and transfected CHO cells. Neurosci. 137: 1347-1358.
     
  5. Chan ASL and Wong YH (2005) Gq-mediated activation of JNK by the GRP receptor is inhibited upon co-stimulation of the Gs-coupled dopamine D1 receptor in Cos-7 cells. Mol. Pharmacol. 68: 1354-1364.
     
  6. Liu AMF and Wong YH (2005) Activation of nuclear factor kB by somatostatin type 2 receptor in pancreatic acinar AR42J cells involves Ga14 and multiple signaling components: A mechanism requiring PKC, CaMKII, ERK and c-Src. J. Biol. Chem. 280: 34617-34625.
     
  7. Wu EHT and Wong YH (2005) Pertussis toxin-sensitive Gi/o proteins are involved in nerve growth factor-induced pro-survival Akt signaling cascade in PC12 cells. Cell. Signal. 17: 881-890.
     
  8. Wu EHT and Wong YH (2005) Involvement of Gi/o proteins in nerve growth factor-stimulated phosphorylation and degradation of tuberin in PC12 cells and cortical neurons. Mol. Pharmacol. 67: 1195-1205.
     
  9. Liu AMF and Wong YH (2004) Activation of nuclear factor kB by the Ga16-coupled adenosine A1 receptor involves c-Src, PKC and ERK signaling. J. Biol. Chem. 279: 53196-53204.
     
  10. Chan AS, Wong YH. (2004) Gbg signaling and calcium mobilization co-operate synergistically in a Sos and Rac-dependent manner in the activation of JNK by Gq-coupled receptors. Cell Signal. 16:823-836.
     
  11. Chan AS, Wong YH. (2004) Epidermal growth factor differentially augments Gi-mediated stimulation of c-Jun N-terminal kinase activity. Br J Pharmacol. 142:635-646.
     
  12. Lo RK, Wong YH. (2004) Signal transducer and activator of transcription 3 activation by the d-opioid receptor via Ga14 involves multiple intermediates. Mol Pharmacol. 65:1427-1439.
     
  13. Ho MK, Chan JH, Wong CS, Wong YH. (2004) Identification of a stretch of six divergent amino acids on the a5 helix of Ga16 as a major determinant of the promiscuity and efficiency of receptor coupling. Biochem J. 380(Pt 2):361-369.
     
  14. Kam AY, Chan AS, Wong YH. (2004) Phosphatidylinositol-3 kinase is distinctively required for m-, but not k-opioid receptor-induced activation of c-Jun N-terminal kinase. J Neurochem. 89:391-402.
     
  15. Kam AY, Chan AS, Wong YH. (2004) k-Opioid receptor signals through Src and focal adhesion kinase to stimulate c-Jun N-terminal kinases in transfected COS-7 cells and human monocytic THP-1 cells. J Pharmacol Exp Ther. 310:301-310.
     
  16. Tian Y, New DC, Yung LY, Allen RA, Slocombe PM, Twomey BM, Lee MM, Wong YH. (2004) Differential chemokine activation of CC chemokine receptor 1-regulated pathways: ligand selective activation of Ga14-coupled pathways. Eur J Immunol. 34:785-795.
     
  17. Hazari A, Lowes V, Chan JH, Wong CS, Ho MK, Wong YH. (2004) Replacement of the a5 helix of Ga16 with Gas-specific sequences enhances promiscuity of Ga16 toward Gs-coupled receptors. Cell Signal. 16:51-62.
     
  18. Lo RK, Cheung H, Wong YH. (2003) Constitutively active Ga16 stimulates STAT3 via a c-Src/JAK- and ERK-dependent mechanism. J Biol Chem. 278:52154-52165.
     
  19. Chan AS, Law PY, Loh HH, Ho PN, Wu WM, Chan JS, Wong YH. (2003) The first and third intracellular loops together with the carboxy terminal tail of the d-opioid receptor contribute toward functional interaction with Ga16. J Neurochem.87:697-708.
     
  20. Wong CS, Ho MK, Wong YH. (2003) The b6/a5 regions of Gai2 and GaoA increase the promiscuity of Ga16 but are insufficient for pertussis toxin-catalyzed ADP-ribosylation. Eur J Pharmacol. 473:105-115.
     
  21. Liu AM, Ho MK, Wong CS, Chan JH, Pau AH, Wong YH. (2003) Ga16/z chimeras efficiently link a wide range of G protein-coupled receptors to calcium mobilization. J Biomol Screen. 8:39-49.
     
  22. Kam AY, Chan AS, Wong YH. (2003) Rac and Cdc42-dependent regulation of c-Jun N-terminal kinases by the d-opioid receptor. J Neurochem. 84:503-513.
     
  23. Kam KW, New DC, Wong YH. (2002) Constitutive activation of the opioid receptor-like (ORL1) receptor by mutation of Asn133 to tryptophan in the third transmembrane region. J Neurochem. 83:1461-1470.
     
  24. Lai FP, Mody SM, Yung LY, Kam JY, Pang CS, Pang SF, Wong YH. (2002) Molecular determinants for the differential coupling of Ga16 to the melatonin MT1, MT2 and Xenopus Mel1c receptors. J Neurochem. 80:736-745.
     
  25. Ho MK, Wong YH. (2001) Gz signaling: emerging divergence from Gi signaling. Oncogene. 20:1615-1625.
     
  26. Ho MK, Wong YH. (2000) The amino terminus of Gaz is required for receptor recognition, whereas its a4/b6 loop is essential for inhibition of adenylyl cyclase. Mol Pharmacol. 58:993-1000.
     
  27. Antonelli V, Bernasconi F, Wong YH, Vallar L. (2000) Activation of B-Raf and regulation of the mitogen-activated protein kinase cascade by the Goa chain. Mol. Biol. Cell. 11:1129-1142.
     
  28. Law PY, Wong YH, and Loh HH. (2000) Molecular mechanisms and regulation of opioid receptor signaling. Ann. Rev. Pharmacol. Toxicol. 40:389-430.
     
  29. Chan JS, Lee JW, Ho MK, and Wong YH. (2000) Preactivation permits subsequent stimulation of phospholipase C by Gi-coupled receptors. Mol. Pharmacol. 57:700-708.
     
  30. Mody SM, Joshi SA, Ho MK, Wong YH. (2000) Incorporation of Gaz-specific sequence at the carboxyl terminus increases the promiscuity of Ga16 toward Gi-coupled receptors. Mol. Pharmacol. 57:13-23.
     
  31. Tsu RC, Ho MKC, Yung LY, Joshi S, Wong YH. (1997) Role of amino and carboxy terminal regions of Gaz in the recognition of Gi-coupled receptors. Mol. Pharmacol. 52:38-45.
     
  32. Tsim ST, Wong JTY, Wong YH. (1997) Calcium ion dependency and the role of inositol phosphates in melatonin-induced encystment of dinoflagellates. J Cell Sci. 110:1387-1393.
     
  33. Tsu RC, Wong YH. (1996) Gi-mediated stimulation of type II adenylyl cyclase is augmented by Gq-coupled receptor activation and phorbol esters treatment. J. Neurosci. 16:1317-1323.

Biotechnology Research Institute Homepage: http://www.ust.hk/~bri/index.html
Molecular Neuroscience Center Homepage: http://www.ust.hk/~mnc/
Central Allocation Grant (CAG) Project website: http://www.ust.hk/~stn/

 

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