David A. Hartley, Ph.D. Assistant Professor Postdoctoral Studies   1999-2001 Boston University 1996-1999 The Salk Institute for Biological Studies Ph.D. 1996 University of Massachusetts Medical Center

Research Interests:  Signal transduction (T lymphocyte transformation; Kinase/phosphatase regulatory mechanisms).

With the sequencing of the human genome completed, an important area of research remaining is an understanding of the regulated interactions of proteins and transmission of signals between them. Two proteins that interact in one cell type may not interact in all cell types or in response to all cellular stimuli. My laboratory studies two specific signal transduction pathways; one leading to T lymphocyte transformation, and one regulating the initiation of protein translation.

Project 1. Herpesvirus saimiri (strain C484M) will induce T cell derived lymphomas and leukemias in most New World primates, New Zealand white rabbits, and can transform human peripheral blood lymphocytes (PBLs) in vitro. H. saimiri is a DNA virus with a large genome encoding 75 open reading frames. Of these 75 open reading frames, only two are required for the induction of T cell transformation. These open reading frames give rise to the Tyrosine kinase Interacting Protein (Tip), and the Saimiri Transforming Protein (STP). Tip will bind to and activate the predominant tyrosine protein kinase in T cells, p56lck. STP has been reported to bind and activate cellular p21ras. One area of focus in my lab is to track all the signaling pathways used by Tip and STP to determine which ones are required to transform T lymphocytes.

Project 2. Rapamycin is a potent immunosuppressant that has now shown promise as an anti-tumor agent. The mammalian target of rapamycin (mTOR) is a large ser/thr protein kinase that is involved in regulating the initiation of protein translation in response to a variety of extracellular signals. The interaction of mTOR with potential substrates is complicated and involves associated docking or adaptor proteins. One potential substrate of mTOR is a protein called alpha4. Alpha4 is a docking subunit of several type2A ser/thr phosphatases (PP2A, PP4, and PP6). Studies in mice have clearly shown that alpha4 is required for at least some of the signals the mTOR transmits leading to the initiation of protein translation. A second area of research in my laboratory examines the mechanisms by which mTOR regulates the activities of ser/thr phosphatases and protein translation.

Representative Publications:

Hartley, D.A., Cooper,G.M. (2002). The Role of mTOR in the Degradation of IRS-1: Regulation of PP2A Activity. J Cell Biochem 85, 304-314.

Hartley, D.A., Amdjadi, K., Hurley, T.R., Lund, T.C., Medveczky, P.G., and Sefton, B.M. (2000). Activation of the Lck tyrosine protein kinase by the Herpesvirus saimiri Tip protein involves two binding interactions. Virology 276, 339-48.

Hartley, D.A., and Cooper, G.M. (2000). Direct binding and activation of the STAT transcription factors by the Herpesvirus saimiri protein Tip. J Biol Chem 275, 16925-32.

Hartley, D.A., Hurley, T.R., Hardwick, J.S., Lund, T.C., Medveczky, P.G., and Sefton, B.M. (1999). Activation of the lck tyrosine protein kinase by the binding of the Tip protein of Herpesvirus saimiri in the absence of regulatory tyrosine phosphorylation. J Biol Chem 274, 20056-9.

Hartley, D.A., and Corvera, S. (1996). Formation of c-Cbl:phosphatidylinositol 3-kinase complexes on lymphocyte membranes by a p56lck-independent mechanism. J Biol Chem 271, 21939-43.

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Last Update 07/30/03
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