Richard Vaillancourt, PhD
The regulation of serine/threonine protein kinase pathways that function in stress-related signal transduction pathways is the research focus in my laboratory. To study these signal transduction pathways, molecular and biochemical approaches are utilized in order to understand the regulatory mechanisms that affect the activity of these kinases. These intracellular serine/threonine protein kinase pathways, which are referred to as mitogen-activated protein (MAP) kinase pathways, are activated by a number of hormones, growth factors, cytokines, and environmental agents.
Currently, at least five MAP kinase pathways have been identified, and there are many protein kinases that function within a defined MAP pathway. One role for these sequential kinase pathways is to transmit an extracellular signal from the plasma membrane to the nucleus. Simply stated, these sequential protein kinase pathways provide the cell with an intracellular signal, which elicits a biological response that is appropriate for the type of stimulus.
The cytoplasmic kinases that transmit the signal from the plasma membrane to various MAP kinase proteins include the MAP/Extracellular signal-regulated kinase (ERK) Kinase Kinase (MEKK) proteins. To date, at least four MEKK proteins have been identified based on a homology to similar protein kinases found in the budding yeast, Saccharomyces cerevisiae. However, the extracellular molecules that regulate the MEKK proteins remain largely undefined in mammalian cells. A major focus in my laboratory is to characterize the role of MEKK3 and MEKK4 in cellular signal transduction pathways.
Current research focuses on the regulation of MEKK3 by the serine/threonine kinase, Akt, which functions in cell survival pathways and the inhibition of apoptosis. In another project we are characterizing the regulation of MEKK4 in response to arsenic in human keratinocytes. Finally, we are also studying the role of the PITSLRE protein kinase in the regulation of tyrosine hydroxylase, as it relates to nicotine signal transduction.
BA, St. Anselm College, Manchester, NH, 1984, Biology
PhD, University of Wisconsin, Madison, 1992, Pharmacology
Seamon, K.B., Vaillancourt, R.R., Edwards, M. and J.W. Daly (1984). Binding of [3H]forskolin to rat brain membranes. Proc. Natl. Acad. Sci. USA 81:5081-5085.
Seamon, K.B., Vaillancourt, R.R. and J.W. Daly (1985). Modulation of forskolin binding to rat brain membranes. J. Cyclic Nucleotide and Prot. Phos. Res. 10:535-549.
Vaillancourt, R.R., Dhanasekaran, N., Johnson, G.L. and A.E. Ruoho (1990). 2-Azido-[32P]NAD+, a photoactivatable probe for G protein structure: Evidence for holotransducin oligomers in which the ADP-ribosylated carboxyl terminus of alpha interacts with both alpha and gamma subunits. Proc. Natl. Acad. Sci. USA 87:3645-3649.
Johnson, G.L., Dhanasekaran, N., Gupta, S.K., Lowndes, J.M., Vaillancourt, R.R. and A.E. Ruoho (1991). Genetic and structural analysis of G protein alpha subunit regulatory domains. J. Cell. Biochem. 47:136-146.
Gardner, A.M., Vaillancourt, R.R. and G.L. Johnson (1993). Activation of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase by G protein and tyrosine kinase oncoproteins. J. Biol. Chem. 268:17896-17901.
Vaillancourt, R.R., Gardner, A.M., Lange-Carter, C.A. and G.L. Johnson (1994). Measuring activation of kinases in the Mitogen-Activated Protein Kinase regulatory network. Meth. Enzymol. 238:258-271.
Conrad, K.E., Oberwetter, J.M., Vaillancourt, R.R., Johnson, G.L. and A. Gutierrez-Hartmann (1994). Identification of the functional components of the Ras signaling pathway regulating pituitary-specific gene expression. Mol. Cell. Biol. 14:1553-1565.
Johnson, G.L. and R.R. Vaillancourt. (1994). Sequential protein kinase reactions controlling cell growth and differentiation. Curr. Opin. Cell Biol. 6:230-238.
Vaillancourt, R.R., Harwood, A.E. and S. Winitz (1994). Analysis of guanine nucleotides associated with the proto-oncogene, Ras. Meth. Enzymol. 238:255-258.
Vaillancourt, R.R., Dhanasekaran, N. and A.E. Ruoho. (1994). Synthesis and use of radioactive photoactivatable NAD+ derivatives as probes for G protein structure. Meth. Enzymol. 237:70-99.
Gardner, A.M., Vaillancourt, R.R., Lange-Carter, C.A. and G.L. Johnson (1994). MEK-1 phosphorylation by MEK kinase, Raf, and MAP kinase: Analysis of phosphopeptides and regulation of activity. Mol. Biol. Cell 5:193-201.
Vaillancourt, R.R., Gardner, A.M. and G.L. Johnson (1994). B-Raf dependent regulation of the MEK-1/MAP Kinase pathway in PC12 cells and regulation by cAMP. Mol. Cell. Biol. 14:6522-6530.
Drummond-Barbosa, D., Vaillancourt, R.R., Kazlauskas, A. and D. DiMaio (1995). Ligand-independent activation of the platelet-derived growth factor beta receptor: requirements for Bovine Papillomavirus E5-induced mitogenic signaling. Mol. Cell. Biol. 15:2570-2581.
Vaillancourt, R.R., Heasley, L.E., Zamarripa, J., Storey, B., Valius, M., Kazlauskas, A. and G.L. Johnson (1995). Mitogen-Activated Protein Kinase Activation is Insufficient for Growth Factor Receptor-Mediated PC12 Cell Differentiation. Mol. Cell. Biol. 15:3644-3653.
Vaillancourt, R.R., Dhanasekaran, N. and A.E. Ruoho (1995). The photoactivatable NAD+ analog, [32P]2-azido-NAD+, defines intra- and intermolecular interactions of the carboxyl-terminal domain of G(alpha)t. Biochem. J. 311:987-993.
Vaillancourt, R.R., Gardner, A.M., Kazlauskas, A. and G.L. Johnson (1996). The kinase-inactive PDGF beta receptor mediates the activation of MAP kinase via the endogenous PDGF alpha receptor in HepG2 cells. Oncogene 13:151-159.
Fanger, G.R., Vaillancourt, R.R., Heasley, L.E., Montmayeur, J.-P.R., Johnson, G.L. and R.A. Maue (1997). Analysis of mutant PDGF receptors expressed in PC12 cells identifies signals governing sodium channel induction during neuronal differentiation. Mol. Cell. Biol. 17:89-99.
Hilborn, M.D., Vaillancourt, R.R., and S.G. Rane. (1998). Growth factor receptor tyrosine kinases acutely regulate neuronal sodium channels through the src signaling pathway. J. Neurosci. 18:590-600.
Fanger, G.R., Widmann, C., Porter, A.C., Sather, S., Johnson, G.L., and R.R. Vaillancourt (1998). 14-3-3 proteins interact with specific MEK kinases. J. Biol. Chem. 273:3476-3483.
Porter, A.C. and R.R. Vaillancourt (1998). Tyrosine kinase receptors and their substrates as oncogenic pathways. Oncogene 17:1343-1352.
Baxter, R.M., Secrist, J.P., Vaillancourt, R.R. and A. Kazlauskas (1998). Full activation of the beta-PDGF-R kinase involves multiple events. J. Biol. Chem. 273:17050-17055.
Porter, A.C., Fanger, G.R. and R.R. Vaillancourt (1999). Signal transduction pathways regulated by arsenate and arsenite. Oncogene 18:7794-7802.
Adams, D.G., Sachs, N.A. and R.R. Vaillancourt (2002). Phosphorylation of the stress-activated protein kinase, MEKK3, at serine 166. Arch. Biochem. Biophys. 407:103-116.
Tran, N.L., Adams, D.G., Vaillancourt, R.R. and R.L. Heimark (2002). Akt Mediates Prostate Carcinoma Survival by Adhesion on N-Cadherin. J. Biol. Chem. 277:32905-32914.
Reierson Draugalis, J., Slack, M.K., Sauer, K.A., Haber, S.L. and R.R. Vaillancourt (2002). Creation and implementation of a learning outcomes document for a doctor of pharmacy curriculum. Amer. J. Pharm. Ed. 66:253-60.
Shi, J., Feng, Y., Goulet, A.-C., Vaillancourt, R.R., Sachs, N.A., Hershey, J.W. and M.A. Nelson (2003). The cyclin dependent kinase CDC2 family member PITSLRE p100 interacts with the p47 subunit of eukaryotic initiation factor 3 during apoptosis. J. Biol. Chem. 278:5062-71.
Lee, T., Huang, Q., Oikemus, S., Shank, J., Ventura, J.-J., Cusson, N., Vaillancourt, R.R., Su, B., Davis, R.J. and M.A. Kelliher (2003). The death domain kinase RIP1 is essential for TNF(alpha) signaling to p38 MAP kinase by recruiting the MAP3K, MEKK3. Mol. Cell. Biol. 23:8377-85.
Sachs, N.A. and R.R. Vaillancourt (2003) Modulation of CDK11P110 Kinase Activity by CK2. Biochimica et Biophysica Acta 1624:98-108.
Mikolajczyk, M., Shi, J., Vaillancourt, R.R., Sachs, N.A. and M.A. Nelson (2003). The cyclin-dependent kinase 11p46 isoform interacts with RanBPM. Biochem. Biophys. Res. Comm. 310:14-8.
Sachs, N.A. and R.R. Vaillancourt (2004) Cyclin Dependent Kinase 11P110 and casein kinase 2 (CK2) inhibit the interaction between tyrosine hydroxylase and 14-3-3. J. Neurochem. 88:51-62.
Bernstein, H., Payne, C.M., Kunke, K., Crowley-Weber, C.L., Waltmire, C.N., Dvorakova, K., Holubec, H., Bernstein, C., Vaillancourt, R.R., Raynes, D.A., Guerriero, V., and H. Garewal (2004). A proteomic study of resistance to deoxycholate-induced apoptosis. Carcinogenesis 25:1-24.
Derbyshire, Z.E., Halfter, U.M., Heimark, R.L. and R.R. Vaillancourt (2005). Angiotensin II stimulated transcription of cyclooxygenase II is regulated by a novel kinase cascade involving Pyk2, MEKK4, and annexin II. Mol. Cell. Biochem 271:77-90.
Halfter, U.M., Derbyshire, Z.E. and R.R. Vaillancourt (2005). Interferon(gamma)-dependent tyrosine phosphorylation of MEKK4 via Pyk2 is regulated by annexin II and SHP2 in keratinocytes. Biochem. J. 388:17-28.
Abell, A.N., Rivera-Perez, J.A., Cuevas, B.D., Uhlik, M.T. Sather, S., Johnson, N.L., Minton, S.K., Lauder, J.M., Winter-Vann, A.M., Nakamura, K., Magnuson, T., Vaillancourt, R.R., Heasley, L.E. and G.L. Johnson (2005). Ablation of MEKK4 kinase activity causes neurulation and skeletal patterning defects in the mouse embryo. Mol. Cell. Biol. 25:8948-8959.
Fritz, A., Brayer, K.J., McCormick, N., Adams, D.G., Wadzinski, B.E. and R.R. Vaillancourt (2006). Phosphorylation of serine 526 is required for MEKK3 and association with 14-3-3 blocks dephosphorylation. J. Biol. Chem. 281: 6236-45.
Stevens, M.V., Parker, P., Vaillancourt, R.R. and T.D. Camenisch (2006). MEKK4 regulates developmental EMT in the embryonic heart. Develop. Dyn. 235:2761-70.