Signal Transduction by the Epidermal Growth Factor Receptor 
protein kinases that we have identified include 
the EGF receptor and the nuclear transcription 
factors expressed by the proto-oncogenes c-myc 
and c-jun. We are investigating the mechanism 
and significance of the phosphorylation of these 
proteins in EGF-treated cells. The overall goal of 
these studies is to establish the molecular details 
of a signal transduction pathway that is initiated 
at the EGF receptor and leads to the regulation of 
nuclear function. 
Tissue Specificity of Tumor Induction 
The gene for the EGF receptor is a frequent site 
of integration by avian leukosis viruses. Insertion 
of the virus causes the expression of a truncated 
EGF receptor. The formation of a virus containing 
a copy of the truncated receptor gene can also 
occur. This truncated gene is the dominantly ac- 
tive oncogene erbB. The primary disease asso- 
ciated with erbB is erythroblastosis. However, 
mutations in the carboxyl terminus of erbB that 
occur during viral replication cause additional 
tumors — fibrosarcomas and angiosarcomas. We 
are studying the molecular basis for the change in 
tissue specificity of the erbB oncogene. 
The approach we are taking is to construct re- 
combinant viruses containing erbB. The advan- 
tage of this procedure is that we can undertake a 
systematic analysis of the effects of erbB muta- 
tions on the tissue specificity of tumor formation. 
The results should help explain why erbB causes 
tumors in one tissue but not in others. This infor- 
mation will be useful in designing strategies for 
clinical intervention in tumor development. 
A hippocampal neuron in primary culture, showing axosomatic and axo- 
dendritic synapses at the surface. The perikaryon and the dendrites of the 
neuron are visualized by immunostain (green fluorescence) for MAP2, a 
protein associated with microtubules of perikarya and dendrites. Presynap- 
tic nerve terminals originating from neurons not visible in the field are 
visualized by immunostain (orange-yellow fluorescence) for the synaptic 
vesicle protein synaptotagmin. 
From the work of Michela Malleoli, Gary Banker, Thomas Siidhof and 
Pietro De Camilli. 
104 
