References:
- Garcia-Mata, R., Dubash, A., Sharek, L., Carr, H.S., Frost, J.A., and Burridge, K. (2007) The nuclear RhoA exchange factor NET1 interacts with proteins of the DLG family, affects their localization and influences their tumor suppressive activity. Mol. Cell. Biol. 27(24), 8683-8697.
- Wu, X. and Frost, J.A. (2006) Multiple Rho Proteins Regulate the Subcellular Targeting of PAK5. Biochem. and Biophys. Res. Com. 351(2), 328-335.
- Qin, H., Carr, H.S., Wu, X., Muallem, D., Tran, D.H., and Frost, J.A. (2005) Characterization of the Biochemical and Transforming Properties of the Neuroepithelioma Transforming Gene 1. J. Biol. Chem. 280 (9), 7603-7613.
- Albert, A.S., Qin, H., Carr, H.S., and Frost, J.A. (2005) PAK 1 Negatively Regulates the Activity of the Rho Exchange Factor Net 1. J. Biol. Chem. 280 (13),12152-12161.
- Tran, N.H., Wu, X. and Frost, J.A. (2005) B-Raf and Raf-1 are Regulated by Distinct Auto regulatory Mechanisms. J. Biol. Chem. 280 (16), 16244-16253
- Tran, N., and Frost, J.A. (2003) Phosphorylation of Raf-1 by PAK1 and Src Regulates Raf-1 Auto inhibition. J. Biol. Chem., 11221-11226.
Jefferey A. Frost, Ph.D.
Associate Professor
UTHSC, Medical School, (713) 500 -6319
Jeffrey.A.Frost@uth.tmc.edu
Signal transduction, cell proloferation and transformation
Research in my laboratory is focused on understanding signaling pathways regulated by Rho family small G proteins that contribute to normal cell proliferation and cancer. These small G proteins function as molecular switches to control various aspects of cell proliferation including cytoskeletal architecture, cell motility and cell cycle progression.
Current studies are aimed at understanding the role of the proto-oncogene Net1 in cell proliferation. Net1 is a RhoA activating protein that shuttles between the nucleus and cytoplasm and is overexpressed in a number of human cancers, including breast cancer. We have recently found that the interaction of Net1 with a number of PDZ domain containing proteins is critically important for its role in proliferation and transformation. Additionally, we have found that the tumor suppressor Dlg1 may be the direct target of Net1 during neoplastic transformation. Dlg1 is a PDZ domain containing molecular scaffold that controls cell polarity and cell cycle progression. Dlg1 is also a critical target for human tumor causing viruses such as HPV and HTLV-1. Ongoing projects in the lab include: a) defining regulatory mechanisms controlling the interaction between Net1 and Dlg1; b) identification of novel Net1 interacting proteins that contribute to its activity in cancer; c) characterization of Dlg1 signaling complexes that allow it to control cell cycle progression; d) exploring the potential for Net1 and Dlg1 expression as prognostic indicators in human breast cancer.
Students working in my laboratory will gain experience in signal transduction as it applies to cell proliferation and transformation. In the course of their studies students will be exposed to a wide variety of molecular, biochemical, and cell biological techniques.
