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| The goal of my laboratory is to understand the molecular mechanism of the formation of the multiprotein signaling complexes that occur after T cell receptor (TCR) activation. | ||||||
| I am interested in understanding the activation and deactivation mechanism of tyrosine kinases and phosphatases and the role that adaptor proteins play in the regulation and creation of these multiprotein signaling complexes. Currently, my laboratory is focused on three main projects. In the first project, we are investigating the sequence of events that occur during the activation of the adaptor protein LAT, the principle nucleation site for the formation of TCR-induced multiprotein signaling complexes. In the second project, we are characterizing the activation mechanism of the tyrosine kinases Pyk2 and Fak and the role these molecules play in TCR-mediated signaling. In the third project, the function of the adaptor proteins Grb2 in TCR-induced signaling pathways and the formation of multiprotein signaling complexes at LAT is being examined. These projects employ a range of techniques from biophysical examination of protein-protein interactions to the use of modern imaging techniques to visualize the trafficking of intracellular signaling proteins to the biochemical characterization of signaling event in human T cells. Together, these studies will provide novel insights into the regulation, formation and function of TCR-induced signaling complexes. This information will prove vital not only for understanding the normal immune response to pathogen infection, but also for providing potential targets for the treatment and cure of debilitating diseases of the human immune system. | ||||||
| Selected Publications | ||||||
| Click Here for a Complete List of Articles | ||||||
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Houtman J.C.D., Houghtling, R.A., Barda-Saad, M., Toda, Y. and Samelson, L.E. Early Phosphorylation Kinetics of Proteins Involved in Proximal T Cell Receptor-Mediated Signaling Pathways. Journal of Immunology, 175:2449-2458, 2005.
Houtman J.C.D., Yamaguchi, H., Barda-Saad, M, Braiman, A., Bowden, B., Appella, E., Schuck, P. and Samelson, L.E. Oligomerization of Signaling Complexes by the Multipoint Binding of Grb2 to both LAT and Sos1. Nature Structural and Molecular Biology, 13:798-805, 2006. Houtman J.C.D., Brown, P.H., Bowden, B., Yamaguchi, H., Appella, E., Samelson, L.E. and Schuck, P. Studying Multi-Site Binary and Ternary Protein Interactions by Global Analysis of Isothermal Titration Calorimetry Data in SEDPHAT: Application to Adaptor Protein Complexes in Cell Signaling. Protein Science, 16:30-42, 2007. Cruz-Orcutt, N. and Houtman J.C.D. PI3 Kinase Function is Vital for the Function but not Formation of LAT-Mediated Signaling Complexes. Molecular Immunology, 46:2274–2283, 2009. Bartelt, R., Cruz-Orcutt, N., Collins, M. and Houtman J.C.D. Comparison of T Cell Receptor-Induced Proximal Signaling and Downstream Functions in Immortalized and Primary T cells. PLoS ONE, 4:e5430, 2009. |
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| Department/Program Affiliations |
| Microbiology |
| Molecular and Cellular Biology |
| Biosciences |