Former SFI Walton Professor and Senior Research Fellow
Smooth Muscle Research Centre
Dundalk Institute of Technology
0429371088Research Interests Research in my laboratory is focused on signal transduction pathways involved in the regulation of smooth muscle contraction. Areas of interest include:
• Mechanisms of Ca2+ sensitization of smooth muscle contraction
• Ca2+-independent phosphorylation of smooth muscle myosin
• Regulation of myosin light chain phosphatase by phosphorylation of the MYPT1 subunit and of the phosphatase inhibitor protein CPI-17
• The mechanism of activation of myosin light chain kinase by Ca2+-calmodulin
• Structural and functional characterization of S100A11, a member of the S100 family of Ca2+-binding proteins
• The roles of the actin-binding proteins, calponin and caldesmon, in the regulation of smooth muscle contraction
• Signaling via the RhoA/Rho-associated kinase pathway in the cerebral vasculature (in collaboration with Dr Don Welsh)
• Regulation of Kv channel function by phosphorylation (in collaboration with Prof Bill Cole)
• Development of highly sensitive proteomic methods for the analysis of myosin isoform expression and myosin phosphorylation in the renal microvasculature (in collaboration with Prof Rodger Loutzenhiser) Publications Swärd, K., Dreja, K., Susnjar, M., Hellstrand, P., Hartshorne, D.J. and Walsh, M.P. (2000) J. Physiol. 522: 33-49. Inhibition of Rho-associated kinase blocks agonist-induced Ca2+ sensitization of myosin phosphorylation and force in guinea pig ileum.
Cole, W.C., Malcolm, T., Walsh, M.P. and Light, P.E. (2000) Circ. Res. 87: 112-117. Inhibition by protein kinase C of the KNDP subtype of vascular smooth muscle ATP-sensitive potassium channel.
Light, P.E., Bladen, C., Winkfein, R.J., Walsh, M.P. and French, R.J. (2000) Proc. Natl. Acad. Sci. U.S.A. 97: 9058-9063. Molecular basis of protein kinase C-induced activation of ATP-sensitive potassium channels.
Deng, J. T., Van Lierop, J. E., Sutherland, C. and Walsh, M. P. (2001) J. Biol. Chem. 276: 16365-16373. Ca2+-independent smooth muscle contraction. A novel function for integrin-linked kinase.
Persad, S., Attwell, S., Gray, V., Mawji, N., Deng, J. T., Leung, D., Yan, J., Sanghera, J., Walsh, M. P. and Dedhar, S. (2001) J. Biol. Chem. 276: 27462-27469. Regulation of protein kinase B/Akt-serine 473 phosphorylation by integrin-linked kinase. Critical roles for kinase activity and amino acids arginine 211 and serine 343.
Thorneloe, K. S., Chen, T. T., Kerr, P. M., Grier, E. F., Horowitz, B., Cole, W. C. and Walsh, M. P. (2001) Circ. Res. 89: 1030-1037. Molecular composition of 4-aminopyridine-sensitive voltage-gated K+ channels of vascular smooth muscle.
Kerr, P. M., Clément-Chomienne, O., Thorneloe, K. S., Chen, T. T., Ishii, K., Sontag, D. P, Walsh, M. P. and Cole, W. C. (2001) Circ. Res. 89: 1038-1044. Heteromultimeric Kv1.2-Kv1.5 channels underlie 4-aminopyridine-sensitive delayed rectifier K+ current of rabbit vascular myocytes.
Wilson, D. P., Sutherland, C. and Walsh, M. P. (2002) J. Biol. Chem. 277: 2186-2192. Ca2+ activation of smooth muscle contraction: evidence for the involvement of calmodulin that is bound to the Triton-insoluble fraction even in the absence of Ca2+.
Van Lierop, J. E., Wilson, D. P., Davis, J. P., Tikunova, S., Sutherland, C., Walsh, M. P. and Johnson, J. D. (2002) J. Biol. Chem. 277: 6550-6558. Activation of smooth muscle myosin light chain kinase by calmodulin: the role of Lys30 and Gly40.
Thorneloe, K. S., Maruyama, Y., Malcolm, A. T., Light, P. E., Walsh, M. P. and Cole, W. C. (2002) J. Physiol. 541: 65-80. Protein kinase C modulation of recombinant ATP-sensitive K+ channels composed of Kir6.1 and/or Kir6.2 expressed with SUR2B.
Mita., M., Yanagihara, H., Hishinuma, S., Saito, M. and Walsh, M. P. (2002) Biochem. J. 364: 431-440. Membrane depolarization-induced contraction of rat caudal arterial smooth muscle involves Rho-associated kinase.
Deng, J. T., Sutherland, C., Brautigan, D. L., Eto, M. and Walsh, M. P. (2002) Biochem. J. 367: 517-524. Phosphorylation of the myosin phosphatase inhibitors, CPI-17 and PHI-1, by integrin-linked kinase.
Dempsey, A. C., Walsh, M. P. and Shaw, G. S. (2003) Structure 11: 887-897. Unmasking the annexin I interaction from the structure of apo-S100A11.
Shiraishi, M., Wang, X., Walsh, M. P., Kargacin, G., Loutzenhiser, K. and Loutzenhiser, R. (2003) FASEB J. 17: 2284-2286. [Full text of express article: 10.1096/fj.03-0096fje]. Myosin heavy chain isoform expression in renal afferent and efferent arterioles: relationship to contractile kinetics and function.
Xiao, B., Sutherland, C., Walsh, M. P. and Chen, S. R. W. (2004) Circ. Res. 94: 487-495. Protein kinase A phosphorylation at serine-2808 of the cardiac Ca2+-release channel (ryanodine receptor) does not dissociate 12.6-kDa FK506-binding protein (FKBP12.6).
Shiraishi, M., Loutzenhiser, R. D. and Walsh, M. P. (2005) Electrophoresis 26: 571-580. A highly sensitive method for quantification of myosin light chain phosphorylation by capillary isoelectric focusing with laser-induced fluorescence detection.
Xiao, B., Jiang, M. T., Zhao, M., Yang, D., Sutherland, C., Lai, F. A., Walsh, M. P., Warltier, D. C., Cheng, H. and Chen, S. R. W. (2005) Circ. Res. 96: 847-855. Characterization of a novel PKA phosphorylation site, serine-2030, reveals no PKA hyperphosphorylation of the cardiac ryanodine receptor in canine heart failure.
Wilson, D. P., Susnjar, M., Kiss, E., Sutherland, C. and Walsh, M. P. (2005) Biochem. J. 389: 763-774. Thromboxane A2-induced contraction of rat caudal arterial smooth muscle involves activation of Ca2+ entry and Ca2+ sensitization: Rho-associated kinase-mediated phosphorylation of MYPT1 at Thr-855 but not Thr-697.
Wilson, D. P., Sutherland, C., Borman, M. A., Deng, J. T., MacDonald, J. A. and Walsh, M. P. (2005) Biochem. J. 392: 641-648. Integrin-linked kinase is responsible for Ca2+-independent myosin diphosphorylation and contraction of vascular smooth muscle.
Xiao, B., Zhong, G., Obayashi, M., Yang, D., Chen, K., Walsh, M. P., Shimoni, Y., Cheng, H., ter Keurs, H. and Chen, S. R. W. (2006) Biochem. J. 396: 7-16. Serine-2030, but not Serine-2808, is the major phosphorylation site in cardiac ryanodine receptor responding to protein kinase A activation upon -adrenergic stimulation in normal and failing hearts.
Galkin, V. E., Orlova, A., Fattoum, A., Walsh, M. P. and Egelman, E. H. (2006) J. Mol. Biol. 359: 478-485. The CH-domain of calponin does not determine the modes of calponin binding to F-actin.
Chen, T. T., Luykenaar, K., Walsh, E. J., Walsh, M. P. and Cole, W. C. (2006) Circ. Res. 99: 53-60. Key role of Kv1 channels in vasoregulation. Grant Income 2006 - 2007 Science Foundation Ireland: ETS Walton Visitor Award
2005 – 2010 Canadian Institutes of Health Research: Mechanisms of regulation of smooth muscle contraction
2004 – 2007 Heart and Stroke Foundation of Alberta, NWT & Nunavut: Vascular smooth muscle S100A11 calcium-binding protein
2003 – 2008 Canadian Institutes of Health Research:
Molecular basis of KV current and its regulation in smooth muscle (Principal Investigator: W.C. Cole; Co-investigator: M.P. Walsh)
2004 – 2007 Canadian Institutes of Health Research:
Rho-kinase regulation of KDR channels in vascular smooth muscle (Principal Investigator: D.G. Welsh; Co-investigator: M.P. Walsh)