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Murine JAK3 is preferentially expressed in hematopoietic tissues and
lymphocyte precursor cells
CB Gurniak and LJ Berg
Department of Molecular and Cellular Biology, Harvard University,
Cambridge, MA 02138, USA.
To elucidate the role of cytokine receptor signal transduction in T- cell
development, we have investigated the expression pattern and biochemical
characteristics of the murine Janus family tyrosine kinase, JAK3. Previous
studies have shown that JAK3 is expressed in lymphoid and myeloid tumor
cell lines and in a small number of lymphoid tissues. To further
characterize JAK3 expression, we used a quantitative polymerase chain
reaction approach to compare JAK3 mRNA levels at multiple stages of T-cell
differentiation and in a broad range of mouse tissues. These studies, in
conjunction with analyses of JAK3 protein expression, show that the highest
levels of JAK3 are in adult, 2-week- old, and fetal thymus, followed by
somewhat lower levels in bone marrow, spleen, fetal liver, and adult
CD4-CD8- thymocytes. We also show that different forms of JAK3 mRNA arise
by alternative splicing. Finally, our biochemical studies show that the
JAK3 kinase domain, but not the pseudo-kinase domain, has tyrosine kinase
activity and, furthermore, that JAK3 kinase activity is abolished by an
amino acid substitution of the conserved lysine in the kinase domain
(K851R). These studies show that JAK3 expression is profoundly skewed to
hematopoietic and lymphoid precursor cells, strongly suggesting a role for
JAK3 in hematopoiesis and T- and B-cell development.
Volume 87,
Issue 8,
pp. 3151-3160,
04/15/1996
Copyright © 1996 by The American Society of Hematology
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