Hsien-yu Wang, Ph.D.
Research Associate Professor
Ph.D. State University of New York at Stony Brook
Department of Physiology and Biophysics
BST, T-5, Rm 180
Phone: 631-444-3489
Fax: 631-444-3432

Our research interest is to study heterotrimeric G-protein-coupled transmembrane signaling, focusing on signaling pathways mediated by Frizzled receptors. One of our studies is to establish the roles of two key inositol polyphosphate (IPP) kinases (IP3K and IPMK) and two protein kinases (CK2 and GSK3) that are essential to the Wnt/b-catenin canonical signaling pathway that links Wnt3a stimulation of IP5 accumulation, to b-catenin stabilization, activation of Lef/Tcf-sensitive transcription, and primitive endoderm formation of mouse F9 embryonal cells, a well-accepted model of signaling in early mouse development. We plan to characterize these two IPP kinases, focusing on their regulation of IP5 production and functional analysis of protein-lipid and protein-protein interactions of these kinases with plasma membrane and canonical scaffolds (especially Dvl/Axin), respectively. Two key downstream protein kinases (CK2 and GSK3) are regulated by IP5. We seek to characterize molecular features of the regulation of CK2 and GSK3 by IP5. The localization and trafficking of these essential kinases, and their dynamic regulation by Wnt3a will be studied.

Most Recent Publications

Lee, Y.-N., Gao, Y. and Wang, H-y. (2008) Differential mediation of the Wnt canonical pathway by mammalian Dishevelleds-1, -2, and -3. Cell. Signal. 20, 443-452.

Ma, L., and Wang, H-y. (2007) Mitogen-activated protein kinase p38 regulates the Wnt/cyclic GMP/Ca²⁺ non- canonical pathway. J. Biol. Chem. 282, 28980-28990.

Gao, Y. and Wang, H-y. (2007) Inositol pentakisphosphate mediates Wnt/b-catenin signaling. J. Biol. Chem. 282, 26490-26502.

Ma L., Wang H-y. (2006) Suppression of cyclic GMP-dependent protein kinase is essential to the Wnt/cGMP/Ca²⁺ pathway. J Biol Chem. 281, 30990-1001.

Gao, Y. and Wang, H-y. (2006) Casein kinase 2 is activated and essential for Wnt/ b-catenin signaling. J. Biol. Chem. 281, 18394-18400.

Wang, H-y., Liu, T., Malbon, C.C. (2006) Structure-function analysis of Frizzleds. Cell Signal. 18,934-941.

Malbon, C.C. and Wang, H-y. (2006) Dishevelled: a mobile scaffold catalyzing development. Curr. Top. Dev. Biol. 72, 153-166.

Wang, H-y.,Tao, J., Shumay, E., and Malbon, C.C. (2006) G-protein coupled-associated A-kinase anchoring protein: AKAP79 and AKAP250. Eur. J. Cell Biol. 85, 643-650.

Yin, D., Gavi, S., Shumay, E. Duell, K., Konopka, J.B., Malbon, C.C., and Wang, H-y., (2005) Successful expression of a functional yeast G-protein-coupled receptor (Ste2) in mammalian cells. Biochem. Biophys. Res.Comm. 329, 281-287.

Wang, H-y., Lee, YN., and Malbon, C.C., (2004) PDE6 is an effector for the Wnt/Ca²⁺/cGMP-signaling pathway in development. Biochem. Soc, Trans. 32, 792-796.

Lee, YN, Malbon, C.C., and Wang, H-y., (2004) Galpha13 signals via p115RhoGEF cascades regulating JNK1 and primitive endoderm formation. J. Ciol.Chem. 279, 54896-54904.

Wang, H-y. (2004) Wnt-Frizzled signaling via cyclic GMP. Front. Biosci. 9, 1043-1047.

Wang, H-y. (2004) Wnt-Frizzled signaling to G-protein coupled effectors. Cell Mol. Life Sci. 61, 69-75.

Li, H., Malbon, C.C., and Wang, H-y (2004) Gene Profiling of Frizzled-1 and Frizzled-2 Signaling: Expression of G-protein-coupled Receptor Chimeras in Mouse F9 Teratocarcinoma Embryonal Cells. Molecular Pharmacology, 65: 45-55.

Wang, H.y. and Malbon, C.C. (2003) Wnt Signaling, Ca²⁺, and Cyclic GMP: Visualizing Frizzled Functions. Science 300:1529-1531.

Wang, H-y., Cheng, Z. and Malbon C.C. (2003) Overexpression of Mitogen-activated Protein Kinase Phosphatases MKPI and MKP2 in Human Breast Cancer. Cancer Lett., 191: 229-237.

Shumay, E., Song, X., Wang, H-y., and Malbon, C. C. (2002) p60 Src mediates insulin-stimulated sequestration of the b₂-adrenergic receptor: Molecular Biology of the Cell , 13, 11: 3943-54.

Ahumada, A., Slusarski, D., Moon, R.T., Malbon, C.C. and Wang, H-y. (2002) Activation of Frizzled-2 signals via cyclic GMP. Science, 298: 2006-2010.

Wang, H-y. (2002) Frizzled-2-receptors. Molecular Page. Alliance for Cell Signaling Website.

Ahumada, A. and Wang, H-y. (2002) Chimeric G-protein-coupled Receptors: Critical New Tools in Drug.Pharmaceutical News, 9, 2-3.

Liu, T., Lee, Y-n., Malbon, C.C. and Wang, H-y. (2002) Activation of the b-catenin/Lef-Tcf pathway is obligate for formation of primitive endoderm by mouse F9 totipotent, teratocarcinoma cells in response to retinoic acid. J. Biol. Chem., 277, 30887-30891.

Huang, X., Song, X., Wang, H-y., and Malbon, C.C. (2002) Expression of constitutively-activated Q227L Gαs in vivo: adaptive changes in expression of regulatory subunits of protein kinase A. Amer. Journal of Physiology, 283: C386-C395.

Doronin, S., Wang, H-y., and Malbon, C.C (2002) Insulin Stimulates Phosphorylation of the b₂-Adrenergic Receptor by the Insulin Receptor Creating a Potent Feedback Inhibitor of its Tyrosine Kinase. J. Biol. Chem., 277: 10698-10703.

Doronin, S., Shumay, E., Wang, H-y., and Malbon, C.C. (2002) Akt mediates sequestration of the b2-adrenergic receptor in response to insulin. J. Biol. Chem., 277:15124-15131.

DeCostanzo, A., Wang, H-y., and Malbon, C.C. (2002) The Frizzled-1/b₂-Adrenergic Receptor Chimera:Pharmacological Properties of a Unique G-Protein-linked Receptor. Archives of Pharmacology, 365: 341-348.

Wang, H.-y., Kanungo, J., and Malbon, C.C. (2002) Expression of Ga(Q226L) induces P19 stem cells to primitive endoderm via MEKK1/4. J. Biol. Chem. 271: 3530-3536.

Huang, X-P., Rosenquist, T.A., Wang, H-y. and Malbon, C.C. (2002) Inducible, tissue-specific suppression of heterotrimeric G protein alpha subunits in vivo. Methods in Enzymology 344:318-327.

Song, X., Tao, J., Huang, X-P., Rosenquist, T.A., Malbon, C.C. and Wang, H-y.(2002) Targeted, regulatable expression of activated heterotrimeric G protein alpha subunits in transgenic mice. Methods in Enzymology. 344: 309-318.

Wang, H-y., Song, X., Huang, X-P. and Tao, J. (2001) Gene Profiling of Transgenic Mice with Targeted Expression of Activated Heterotrimeric G Protein Alpha Subunits using DNA Microarray. Methods in Enzymology, 345:529-539.

Doronin, S., Shumay, E., Wang, H-y., and Malbon, C.C. (2001) Lithium Suppresses Signaling and Induces Rapid Sequestration of Beta2-Adrenergic Receptors Biochem. Biophys. Res. Commu.,288:150-155.

Malbon, C.C., Wang, H-y., and Moon, R.T. (2001) Wnt Signaling and Hetertrimeric G-proteins: Strange Bedfellows or a Classic Romance. Biochem. Biophys. Res. Commu. 287:589-593.

Song, X., Zheng, X., Malbon, C.C. and Wang, H-y. (2001) Gαi2 enhances in vivo activation of and insulin signaling to GLUT4. J. Biol. Chem., 276: 34651-34658.

Tao, J., Malbon, C.C. and Wang,H-y. (2001) Gai2 enhances insulin signaling via suppression of protein tyrosine phosphatase 1B. J. Biol. Chem., 276: 39705-39712.

Tao, J., Malbon, C. C., and Wang, H-y. (2001)Insulin stimulates tyrosine phosphorylation and inactivation of protein tyrosine phosphatase 1B in vivo. J. Biol. Chem., 276:29520-29525.

Fan, G-f., Shumay, E., Wang, H-y., and Malbon, C.C. (2001) The Scaffold Protein Gravin (AKAP250) binds the Beta2- adrenergic Receptor Via the Receptor Cytoplasmic R329 to L413 Domain and Provides a Mobile Scaffold During Desensitization. J. Biol. Chem., 276: 24005-24014.

Liu, T., DeCostanzo, A. J., Liu, X., Wang, H-y., Hallagan, S., Moon, R.T. and Malbon, C.C. (2001)Heterotrimeric G-proteins Go and Gq mediate signaling from activation of rat Frizzled-1 to the b-catenin/Lef-Tcf pathway in development. Science, 292: 1718-1722.

Fan, F., Shumay, E., Malbon, C. C. and Wang, H-y. (2001) c-Src tyrosine kinase binds the b2-adrenergic receptor via phospho-Tyr350, phosphorylates GRK2, and mediates agonist-induced receptor desensitization. J. Biol. Chem.,276: 13240-13247.

Doronin, S., Lin F., Wang, H-y. and Malbon, C.C. (2000) Phosphorylation of the C-terminal, Cytosolic Domain of the b-adrenergic Receptor by Protein Kinase A is Allosterically Regulated by Disulfide Bond Formation. Protein Expression, 20 (3):451-461.

Wang, H-y., Doronin, S., and Malbon, C.C. (2000) Insulin Activation of Mitogen-activated Protein Kinases Erk1,2 is Amplified via Beta-adrenergic Receptor Expression and Requires the Integrity of the Tyr350 of the Receptor. J. Biol. Chem., 275, 36086-36093.

Kanungo, J., Potapova, I., Malbon, C. C., and Wang, H-y. (2000) Retinoic Acid-induced Differentiation of P19 Embryonal Carcinoma Stem Cells is Mimicked by Constitutively-active MEKK4 and MEKK1, but Blocked Only by the Dominant Negative Mutant of MEKK4. J. Biol. Chem., 275, 24032-24039.