David K. Ann
Molecular Pharmacology and Toxicology
Norris Comprehensive Cancer Center
Center for Craniofacial Molecular Biology
Gene Expression and Signal Transduction
Our laboratory is interested in understanding the molecular mechanism(s) underlying cell proliferation and tissue-specific gene expression using epithelial cells as a model system. To this end, we are employing state-of-the-art molecular approaches to elucidate the interplay among various cis-elements and trans-factors and the signal transduction pathways.
Members of the Raf family of protein kinases are believed to be essential components of cell signaling machinery that mediates diverse responses to extracellular stimuli in eukaryotic cells. The sequential activation of Raf/MEK/MAP kinase cascade has been demonstrated to play an important role in initiation of cellular proliferation, differentiation and oncogenic transformation. Our studies have demonstrated that the activator of this Raf/MEK/MAP kinase cascade is necessary for regulating salivary acinar epithelial cells hyperplasia and hypertrophia by b-receptor agonist. Studies are also initiated to identify the target gene(s) whose expression is regulated directly or indirectly by Raf-1 kinase.
By combining molecular biological and biochemical procedures, these studies promise to provide novel insights into molecular mechanism(s) governing cell differentiation, proliferation and gene expression.
- Lin, H.H., Li, W.-Y. and Ann, D.K. (1993) The helix-loop-helix proteins, SCBPs, can modulate cAMP inducible RP4 gene expression in the salivary cells. J. Biol. Chem. 268, 10214-10220.
- Reddy, S.P.M., Chuu, Y.-J., Lao, P.N., Donn, J., Ann, D.K. and Wu, R. (1995) Expression of human squamous cell differentiation marker, spr1, in tracheobronchial epithelium depends on Jun and TRE motifs. J. Biol. Chem. 270, 26451-26459.
- Lin, H.H., Tu, Z-J. and Ann, D.K. (1996) Involvement of nuclear orphan receptor NGFI-B in transcriptional activation of salivary-specific R15 gene by cAMP. J. Biol. Chem. (accepted).