expressed primarily in myeloid cells, particularly 
granulocytes. As in the case of p56''^^, mutation of a 
carboxyl-terminal phosphorylation site unmasks 
the transforming ability of p59*'^*. Since p59*'^* is 
maximally expressed in terminally differentiated 
cells, it almost certainly regulates aspects of my- 
eloid cell function unrelated to replication. Prelimi- 
nary studies suggest that p59*'^^ is involved in the 
control of cytokine release. Current attempts to de- 
fine the functions of p56'^'^, p59*"^, and p59*^^ in- 
volve the use of transgenic animals to alter the nor- 
mal pattern of expression of these kinases and the 
use of retroviral vectors to introduce activated ver- 
sions of these signaling molecules into experimen- 
tally manipulable cell lines. 
III. The Ick Promoter System as a Tool for Investi- 
gating T Cell Development. 
Both promoters of the Ick gene are lymphocyte- 
specific transcriptional regulatory elements. How- 
PUBLICATIONS 
ever, although the upstream promoter is active in 
essentially all T cells, the downstream promoter is 
expressed almost exclusively in thymocytes. These 
two regulatory elements function appropriately in 
transgenic animals and hence can be variously used 
to investigate features of normal T cell develop- 
ment. For example, four lines of animals bearing 
the downstream Ick promoter coupled to SV40 
large T antigen have been propagated for more 
than a year. These animals predictably develop thy- 
momas with a latency of —18 wk. Remarkably, cells 
from these thymic tumors can be readily propa- 
gated in vitro and in many cases appear to follow a 
normal differentiative program during continuous 
culture. Analysis of these cell lines may permit the 
identification of genes involved in the intrathymic 
maturation of T cells. 
Dr. Perlmutter is also Associate Professor of Medi- 
cine and of Biochemistry at the University of Wash- 
ington School of Medicine. 
Books and Chapters of Books 
Perlmutter, R.M., Schroeder, H.W, Jr., and Hillson, J.L. 1988. Diversification of the human fetal antibody rep- 
ertoire. In B Cell Development, UCLA Symposia on Molecular and Cellular Biology (Witte, O.N., Klinman, 
N.R., and Howard, M.C., Eds.). New York: Liss, pp 91-104. (New Ser 85.) 
Articles 
Louie, R.R., King, C.S., MacAuley A., Marth, J.D., Perlmutter, R.M. , Eckhart, W, and Cooper, J.A. 1988. p56^'=^ 
protein-tyrosine kinase is cytoskeletal and does not bind to polyomavirus middle T antigen. / Virol 
62:4673-4679. 
Marth, J.D., Lewis, D.B., Cooke, M.P., Mellins, E.D., Gearn, M.E., Samelson, L.E., Wilson, C.B., Miller, A.D., 
and Perlmutter, R.M. 1988. Lymphocyte activation provokes modification of a lymphocyte-specific protein 
tyrosine kinase (p56''^^. J Immunol 142:2430-2437. 
Perlmutter, R.M. 1989. T cell signaling. Science 245:344. 
Perlmutter, R.M., Marth, J.D., Ziegler, S.F., Garvin, A.M., Pawar, S., Cooke, M.E, and Abraham, K.M. 1988. Spe- 
cialized protein tyrosine kinase proto-oncogenes in hematopoietic cells. Biochim Biophys Acta 948:245- 
262. 
Perlmutter, R.M., Manh, J.D., Lewis, D.B., Peet, R., Ziegler, S.F., and Wilson, C.B. 1988. Structure and expres- 
sion of Ick transcripts in human lymphoid cells. / Cell Biochem 38:117-126. 
Sartor, O., Gregory, F.S., Templeton, N.S., Pawar, S., Perlmutter, R.M., and Rosen, N. 1989. Selective expres- 
sion of alternative Ick mRNAs in human malignant cell lines. Mol Cell Biol 9:2983-2988. 
Schroeder, H.W, Jr. , Walter, M.A., Hofker, M.H., Ebens, A. , Willems van Dijk, K., Liao, L.C., Cox, D.W, Milner, 
E.C.B., and Perlmutter, R.M. 1988. Physical linkage of a human immunoglobulin heavy chain variable re- 
gion gene segment to diversity and joining region elements. Proc Natl Acad Sci USA 85:8196-8200. 
Willems van Dijk, K., Schroeder, H.W, Jr. , Perlmutter, R.M. , and Milner, E.C.B. 1988. Heterogeneity in the 
human Ig Y^i locus. J Immunol 142:2547-2554. 
Continued 
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