molecules, prostaglandin and prostacyclin. Col- 
laborative studies with Dr. Michael Gelb (University 
of Washington) have led to the identification of a 
new type of protein modification in animal cells. 
Lamin B, a nuclear protein from human cancer 
cells, was shown to contain a farnesyl group. Exper- 
iments are under way to explore the potential role 
of this modification in mediating the attachment of 
lamin B to the nuclear membrane. 
The laboratory of Investigator Vann Bennett, 
M.D., Ph.D. (Duke University) is engaged in studies 
on ankyrin, a versatile family of proteins that partic- 
ipate in the placement of a variety of membrane 
proteins in specialized domains of the plasma mem- 
brane. The ankyrin family includes members with 
distinct localization and membrane receptors. One 
isoform of ankyrin found in brain is confined to the 
nodes of Ranvier and may play a role in the local- 
ization of voltage-dependent sodium channels to 
this region— an essential requirement for impulse 
conduction in myelinated nerve fibers. The diversity 
of ankyrins results in part from multiple genes, two 
of which have been cloned from human brain, and 
in part from alternative splicing of mRNA. The rec- 
ognition site of ankyrin for one membrane protein 
has been narrowed to a region containing an evolu- 
tionarily ancient sequence motif also found in cer- 
tain yeast and Drosophila proteins that are in- 
volved in the regulation of development. 
Cells in the body are attached to adhesive pro- 
teins through cell surface receptors called integrins. 
This attachment is vital for proper cellular organiza- 
tion, structure, and metabolism and plays an im- 
portant role in embryogenesis. The laboratory of 
Investigator Richard O. Hynes, Ph.D. (Massachu- 
setts Institute of Technology) is involved in studies 
of several of the adhesive proteins, especially the 
fibronectins. Progress is reported in understanding 
1) alterations of fibronectins and integrins in tumor 
cells, 2) the involvement of certain integrins in he- 
mostasis and thrombosis, and 3) alterations in 
fibronectins during wound healing. The molecular 
details of these proteins and their roles in normal 
physiology and various pathological conditions 
continue to be examined. 
The product of one proto-oncogene, platelet-de- 
rived growth factor (PDGF) , stimulates cell prolifer- 
ation by first binding to its receptor on the cell sur- 
face. Investigator Lewis T. Williams, M.D., Ph.D. 
(University of California at San Francisco) and his 
colleagues have studied the mechanism by which 
the surface receptor sends signals to the nucleus of 
the cell. This year they identified several of the sig- 
naling molecules with which the receptor interacts 
directly. These signaling enzymes include Raf-1, 
phosphatidylinositol kinase, and phospholipase C. 
For the first time this group has been able to use 
highly purified components to reconstruct the in- 
teractions between the receptor and the signaling 
molecules in cell-free systems. 
Another polypeptide growth factor that triggers 
cell division by binding to a specific cell surface re- 
ceptor and activating its tyrosine-specific protein 
kinase activity is studied by Investigator Charles J. 
Sherr, M.D., Ph.D. (St. Jude Children's Research 
Hospital). The growth factor in question is colony- 
stimulating factor- 1 (CSF-1), whose receptor is en- 
coded by a gene genetically linked to the gene for 
the PDGF receptor, the two genes having arisen by 
duplication and subsequent evolutionary diver- 
gence. Specific mutations in the CSF-1 receptor 
gene (c-fms proto-oncogene) were found to acti- 
vate its kinase activity in the absence of CSF-1, 
thereby providing sustained signals for cell growth 
that lead to tumor formation. Because expression 
of the CSF-1 receptor is normally restricted to 
blood monocytes and tissue macrophages, such 
mutations might etiologically contribute to the de- 
velopment of myeloid leukemia. 
Associate Investigator Linda J. Pike, Ph.D. (Wash- 
ington University) is also interested in the mecha- 
nism of action of growth factors. Work in her labo- 
ratory has shown that the activity of an intracellular 
enzyme, a phosphatidylinositol kinase, is stimu- 
lated in response to epidermal growth factor (EGF). 
This enzyme has been purified, and recombinant 
DNA technology is being used to clone the enzyme. 
Other studies have shown that prolonged treat- 
ment of cells with EGF renders them insensitive to 
further stimulation by the growth factor, a phenom- 
enon termed desensitization. The cell surface re- 
ceptor for EGF is a single polypeptide chain. Upon 
binding of EGF, two polypeptide chains associate to 
form a receptor dimer and mediate the biological 
effects of the hormone. In desensitized cells, EGF 
receptor dimer formation is blocked, which may ac- 
count for the inability of the cells to respond to the 
growth factor. 
Investigator Mary-Jane Gething, Ph.D. (University 
of Texas Southwestern Medical Center at Dallas) 
and her colleagues study the molecular genetics of 
membrane and secretory proteins. Experiments 
focus on three proteins: 1) the hemagglutinin of in- 
fluenza virus, which is being utilized as a marker 
molecule for specific cell populations in transgenic 
mice produced in an attempt to establish an animal 
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