OHase —65 element. Collectively these results 
identify a cellular promoter that is regulated by 
NGFI-B and implicate this nuclear receptor in the 
transcriptional induction of 21-OHase by ACTH. 
The investigations of SF-1 and NGFI-B highlight 
the critical role of nuclear receptors in the regula- 
tion of the steroidogenic enzymes. This role is of 
significant interest for several reasons. First, the 
great potential for competition and/or cooperation 
between various nuclear receptors provides a possi- 
ble mechanism for implementing the complex regu- 
latory circuits that control steroidogenic enzyme 
expression. In addition, the link between orphan 
receptor action and control of steroidogenic en- 
zyme gene expression raises the exciting possibility 
that metabolic intermediates of steroid products 
may serve as ligands for these orphan receptors. 
Dr. Parker is also Associate Professor of Medi- 
cine and Biochemistry at Duke University Medical 
Center and attending physician at Duke Univer- 
sity Medical Center. 
Articles 
Domalik, L.J., Chaplin, D.D., Kirkman, M.S., Wu, 
R.C., Liu, W., Howard, T.A., Seldin, M.F., and 
Parker, K.L. 1991. Different isozymes of mouse 
1 1/3- hydroxylase produce mineralocorticoids and 
glucocorticoids. Mol Endocrinol 5:1853-1861. 
Lala, D.S., Rice, D.A., and Parker, K.L. 1992. Ster 
oidogenic factor I, a key regulator of steroido- 
genic enzyme expression, is the mouse homolog 
of fushi tarazu-factor I. Mol Endocrinol 6:1249- 
1258. 
Tremblay, A., Parker, K.L., and Lehoux, J.G. 1992. 
Dietary potassium supplementation and sodium 
restriction stimulate aldosterone synthase but not 
1 li8-hydroxylase P-450 messenger ribonucleic 
acid accumulation in rat adrenals and require 
angiotensin II production. Endocrinology 
130:3152-3158. 
MECHANISM OF ACTION OF POLYPEPTIDE GROWTH FACTORS 
Linda J. Pike, Ph.D., Associate Investigator 
Dr. Pike is interested in the control of cell growth. 
In particular, her research focuses on the mecha- 
nism by which epidermal growth factor (EGF) trans- 
mits its signal across the cell membrane. Binding of 
EGF to the extracellular domain of its cell surface 
receptor stimulates a protein-tyrosine kinase ac- 
tivity located on the intracellular domain of the 
receptor. Other biological processes, including 
phosphatidylinositol (PI) turnover and receptor in- 
ternalization, are also stimulated by ligand binding. 
Although the binding of EGF stimulates numerous 
responses, prolonged treatment of cells with EGF 
leads to a loss of responsiveness of the cells to the 
growth factor, a process known as desensitization. 
The current goals are 1) to understand the regula- 
tion of phosphoinositide metabolism and its role in 
signal transduction and 2) to elucidate the molecu- 
lar mechanism of EGF receptor desensitization. 
Phosphoinositide Metabolism 
Phosphatidylinositol 4-kinase. Previous work 
from the laboratory has shown that EGF stimulates 
the activity of a PI 4-kinase in A431 cells, a human 
epidermal carcinoma cell line. The EGF-stimulated 
PI 4-kinase was purified from A43 1 cells and shown 
to be a monomeric protein with a molecular weight 
of 55,000. PI 4-kinase was also purified from human 
placenta, and the amino acid sequences of two tryp- 
tic peptides from the purified enzyme were deter- 
mined. Based on the sequence of the longer peptide 
(40 amino acids), a unique 45-bp oligonucleotide 
probe was synthesized and used to screen a Xgtl 1 
human placenta cDNA library. 
Approximately 500,000 independent isolates 
were screened, and 13 positive clones for PI 4- 
kinase were identified. The 2.3-kb insert from one 
of the clones was sequenced and found to encode a 
protein that contained the sequence of both pep- 
tides determined by direct protein sequencing. The 
predicted protein has a molecular weight of 
61 ,000. The cDNA for the PI 4-kinase was expressed 
in Escherichia coli as a fusion protein with gluta- 
thionine 5'-transferase . Assay of E. coli lysates demon- 
strated the presence of increased PI 4-kinase activity 
102 
