MURINE JAK3 IS PREFERENTIALLY EXPRESSED IN HEMATOPOIETIC TISSUES AND LYMPHOCYTE PRECURSOR CELLS

To elucidate the role of cytokine receptor signal transduction in T-ce ll development, we have investigated the expression pattern and bioche mical characteristics of the murine Janus family tyrosine kinase, JAK3 . Previous studies have shown that JAK3 is expressed in lymphoid and m yeloid tumor cell lines and in a small number of lymphoid tissues. To further characterize JAK3 expression, we used a quantitative polymeras e chain reaction approach to compare JAK3 mRNA levels at multiple stag es of T-cell differentiation and in a broad range of mouse tissues. Th ese studies, in conjunction with analyses of JAK3 protein expression, show that the highest levels of JAK3 are in adult, 2-week-old, and fet al thymus, followed by somewhat lower levels in bone marrow, spleen, f etal liver, and adult CD4(-)CD8(-) thymocytes. We also show that diffe rent forms of JAK3 mRNA arise by alternative splicing. Finally, our bi ochemical studies show that the JAK3 kinase domain, but not the pseudo -kinase domain, has tyrosine kinase activity and, furthermore, that JA K3 kinase activity is abolished by an amino acid substitution of the c onserved lysine in the kinase domain (K851R). These studies show that JAK3 expression is profoundly skewed to hematopoietic and lymphoid pre cursor cells, strongly suggesting a role for JAK3 in hematopoiesis and T- and B-cell development. (C) 1996 by The American Society of Hemato logy.