gesting that only the lAPP portion is hormonally ac- 
tive. The chromosomal gene that encodes lAPP is 
located in the pl2.3 region of chromosome 12. 
Studies are under way to determine whether insu- 
lin and lAPP are synthesized and released in a coor- 
dinate fashion and whether there may be differ- 
ences in the expression of lAPP and insulin under 
certain conditions. 
III. Insulin Receptor Expression and Maturation. 
To generate sufficient amounts of human insulin 
receptor-related materials for studies of its three-di- 
mensional structure and insulin-binding region, Dr. 
Steiner and his colleagues explored several systems 
for the overproduction of the receptor. One of 
these, the baculovirus system, utilizes insect cells 
and viral vectors to overproduce proteins of inter- 
est. Suitable vectors have been constructed for the 
expression of the insulin holoreceptor, as well as 
truncated versions in which the transmembrane 
and internal regions have been deleted from the P- 
subunit so that a soluble form of the receptor is se- 
creted from the cells. Very high levels of expression 
of normal and mutated insulin receptors have also 
been obtained using dihydrofolate reductase 
(DHFR) -vector systems that are suitable for expres- 
sion in animal cells such as the CHO (Chinese ham- 
ster ovary) cell line. Among receptor mutants being 
studied using these systems are several involving 
the proteolytic cleavage site of the a/^-proreceptor 
PUBLICATIONS 
in which the tetrabasic cleavage recognition se- 
quence has been systematically modified by the re- 
placement of individual basic residues with ala- 
nines. Recent studies from this laboratory have 
indicated that the insulin-binding region in the re- 
ceptor is located near the amino terminus of the a- 
subunit, probably somewhere within the first 100 
amino acids. 
IV Evolution of Insulin and Insulin Receptor 
Molecules. 
The evolution of insulin and insulin-like growth 
factors (IGFs) and the coevolution of the insulin 
and IGF receptor molecules are currently being ex- 
plored in a variety of vertebrate and/or nonverte- 
brate species. Several cDNAs encoding IGF-like 
molecules from both the coho salmon (a teleost 
fish) and the hagfish (a jawless vertebrate) have 
now been identified. The salmon IGF-I-like peptide 
appears to be under growth hormone control. 
These studies will be extended to protochordate 
species such as Amphioxus. The conservation of 
features in insulin and IGF receptors that are be- 
lieved to be important for binding of insulin or IGF 
in various vertebrate species is also being studied, 
using PGR methods to amplify appropriate regions. 
Dr. Steiner is also the A. N. Pritzker Distinguished 
Service Professor of Biochemistry and Molecular Bi- 
ology and of Medicine at The University of Chicago. 
Books and Chapters of Books 
Sanke, T, Nishi, M., Steiner, D.F., and Bell, G.I. 1989. Sequence of a human insulinoma cDNA encoding islet 
amyloid polypeptide: a mediator of (S-cell dysfunction in diabetes? In Perspectives on the Molecular Biol- 
ogy and Immunology of the Pancreatic ^Cell (Hanahan, D., McDevitt, H.O., and Cahill, G.F., Eds.). Cold 
Spring Harbor, NY: Cold Spring Harbor, pp 49-54. 
Steiner, D.F. , Bell, G.I. , Hammer, R.E. , Madsen, O.D., Carroll, R.J. , and Chan, S.J. 1989- Cellular and molecu- 
lar biology of the (3 cell: an overview. In Perspectives on the Molecular Biology and Immunology of the 
Pancreatic ^Cell (Hanahan, D., McDevitt, H.O., and Cahill, G.F. , Eds.). Cold Spring Harbor, NY: Cold 
Spring Harbor, pp 19-36. 
Steiner, D.F., Bell, G.I., and Tager, H.S. 1989. Chemistry and biosynthesis of pancreatic protein hormones. In 
Endocrinology (DeGroot, L., Ed.). Philadelphia, PA: Saunders, pp 1263-1289. 
Articles 
Carroll, R.J., Hammer, R.E., Chan, S.J., Swift, H.H., Rubenstein, A.H., and Steiner, D.F. 1988. A mutant human 
proinsulin is secreted from islets of Langerhans in increased amounts via an unregulated pathway. Proc 
Natl Acad Set USA 85:8943-8947. 
Continued 
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