Jacqueline Stephens

Professor
Ph.D., East Carolina University School of Medicine, 1992

Cell biology; insulin action in adipocytes and the regulation of transcription factors during adipogenesis.

jsteph1@lsu.edu

My current area of interest is to examine the regulation, activation and function of STATs (Signal Transducers and Activators of Transcription) in adipocytes. The STAT family of mammalian transcription factors is comprised of seven proteins (STATs 1, 2, 3, 4, 5A, 5B, and 6) which, in response to stimulation of various receptors, mainly those for cytokines, are phosphorylated on tyrosine residues causing their translocation to the nucleus. Each STAT family member shows a distinct pattern of activation by cytokines and upon nuclear translocation can regulate the transcription of particular genes. The order of events for STAT activation can be briefly described as follows: 1) Ligand binding of cell surface receptor; 2) Receptor association with a JAK (Janus Kinase) family member; 3) JAK tyrosine phosphorylation of STAT proteins; 4) Dimerization of the STATs; 5) Translocation to the nucleus; and 6) DNA binding. STATs have been shown to bind distinct DNA sequences, and this binding regulates the transcription of specific genes. Additionally, STATs can be activated independently of JAK kinases, and serine phosphorylation may also contribute to the ability of STATs to regulate transcription.

STATs have cell specific functions, and we hypothesize that these transcription factors play a key role in the regulation of genes involved in lipid metabolism and possibly in regulating genes which confer insulin sensitivity to the adipocyte. To test these hypotheses, we are examining the regulation and activation of STATs in adipocytes by growth factors which we have recently demonstrated to be potent and specific activators of STATs 1, 3, 5A, and 5B in adipocytes. These studies will allow us to identify the function of STATs in adipocytes by identifying the target genes which are transcriptionally regulated by these proteins. We predict that these studies will lead to insights into the molecular mechanisms regulating energy homeostasis and may contribute to understanding the defects underlying obesity and type II diabetes.

Stewart, W.C. Morrison, R.F., Young, S., and Stephens, J.M. (1999) Regulation of STATs by effectors of adipogenesis: Coordinate regulation of STATs 1, 5A, and 5B with PPARgamma and C/EBPalpha. Biochem. Biophys. Acta. (In press)

Stephens, J. M., Morrison, R.F., Wu, Z., and Farmer, S.R. (1999) PPAR ligand dependent induction of STATs 1 and 5 during adipogenesis. Biochem. Biophys. Res. Commun. 262, 216-222.

Stephens, J. M., Lumpkin, S. J. and Fishman, J.B. (1998) Activation of STATs 1 and 3 by LIF, OSM, and IFN in Adipocytes. J. Biol. Chem. 273, 31408-31416

Balhoff, J.P. and Stephens, J.M. (1998) Highly specific and quantitative activation of STATs in adipocytes. Biochem. Biophys. Res. Commun. 247, 894-900.

Stephens, J.M., Lee, J., and Pilch, P.F. (1997) TNF-induced insulin resistance in 3T3-L1 adipocytes is accompanied by a loss of IRS-1 and GLUT4 expression without a loss of insulin receptor-mediated signal transduction. J. Biol. Chem. 272, 971-976.

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