mains unclear. To examine this question, Dr. Yau's 
group has used peptide antibodies against various 
known G protein j3 and 7 subunits to stain the retina. 
The rod and cone cells show different immunostain- 
ings for ^ and 7 subunits; essentially, rod outer seg- 
ments appear to have and 7j subunits, while cone 
outer segments appear to have 1S3 and 72 subunits. 
These findings suggest that (3 and 7 subunits proba- 
bly also contribute to the functional characteristics 
of transducin, and may partially account for the dif- 
ferent light response properties of rods and cones. 
Part of the above work was supported by a grant 
from the National Eye Institute, National Institutes 
of Health. 
Dr. Yau is also Professor of Neuroscience at the 
fohns Hopkins University School of Medicine. 
Books and Chapters of Books 
Yau, K.-W., and Haynes, L.W. 1991 • Gating kinetics 
of the cGMP-activated conductance of retinal 
cones. In Signal Transduction in Photoreceptor 
Cells (Hargrave, P.A., Hofmann, K.P., and Kaupp, 
U.B., Eds.). Berlin: Springer-Verlag, pp 175-179. 
Articles 
Dhallan, R.S., Macke, J.P., Eddy, R.L., Shows, T.B., 
Reed, R.R., Yau, K.-W., and Nathans, J. 1992. 
Human rod photoreceptor cGMP-gated channel: 
amino acid sequence, gene structure, and func- 
tional expression. /A^ewrosc? 12:3248-3256. 
Yau, K.-W., Nakatani, K., and Tamura, T. 1991. 
Sodium-calcium exchange and phototransduction 
in retinal photoreceptors. Ann NY Acad Set 
639:275-284. 
REGULATION OF CELL ACTIVITY BY TRANSMEMBRANE SIGNALS 
Edward B. Ziff, Ph.D., Investigator 
Dr. Ziff's laboratory studies the molecular mecha- 
nisms by which growth factors and other transmem- 
brane signaling agents control cellular proliferation 
and differentiation. They have shown that grovia;h 
factors rapidly induce the transcriptional activity of 
specific genes, including the c-fos gene, which en- 
codes the transcription factor c-Fos, the prototype 
of the family of early- response proteins. The c-Fos 
protein forms a heterodimeric complex with c-Jun 
protein, which binds to specific DNA sequences and 
activates transcription of neighboring genes. 
For these studies. Dr. Ziff's laboratory employs 
the rat pheochromocytoma cell line PCI 2, which 
responds to the polypeptide hormone nerve growth 
factor (NGF) by differentiating from a chromafifin- 
like to a neuronal phenotype. They find that NGF 
rapidly induces c-fos in PCI 2. The mechanism of 
induction is being investigated in studies supported 
by the American Cancer Society. The fact that c-Fos 
protein is a transcription factor and is controlled by 
NGF suggests it has a role in regulating gene ex- 
pression and neuronal differentiation in response 
to NGF. 
Following the rapid induction of c-fos by NGF, 
other genes are induced with slower kinetics. One is 
the tyrosine hydroxylase (TH) gene, a delayed-early 
gene induced 1-2 h after NGF treatment that en- 
codes an enzyme that catalyzes the rate-limiting step 
of catecholamine neurotransmitter biosynthesis. Dr. 
Ziff's laboratory has identified a TH promoter regula- 
tory sequence, the TH-FSE, which binds the Fos-Jun 
complex and is required for NGF induction of tran- 
scription of the TH gene. This indicates that NGF 
induction of c-Fos regulates transcription of the TH 
gene, thereby providing a mechanism for NGF con- 
trol of catecholamine biosynthesis. Other stimuli 
that activate c-Fos, such as Ca^^ ion influx following 
depolarization of neurons, may also regulate TH 
gene expression through this pathway. The c-Fos 
protein belongs to a family of proteins, including 
FosB, Fral, and Fra2, all of which may bind tojun or 
to members of the Jun protein family. The resulting 
complexes in turn may all bind to the same DNA 
element. The different c-Fos family members differ 
in their patterns of expression following cell stimu- 
lation, as well as in their structures outside the DNA- 
binding domains, suggesting they may regulate gene 
activity differentially when complexed with a DNA 
element such as the TH ESE. Recent studies in the 
Ziff laboratory indicate that the TH gene is repressed 
by a mechanism in which the c-Fos protein, an acti- 
vator, is replaced by a different c-Fos family 
member, which serves as a repressor. Indeed, other 
Eos family members, including FosB, become the 
predominant species as c-Fos levels dwindle and TH 
transcription is shut off. 
Another gene induced with a late time course, the 
peripherin gene, encodes a neuronal-specific type 
NEUROSCIENCE 449 
