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Carboxyl-Truncated STAT5 Is Generated by a Nucleus-Associated
Serine Protease in Early Hematopoietic Progenitors
Johann Meyer,
Manfred Jücker,
Wolfram Ostertag, and
Carol Stocking
From the Department of Cell and Virus Genetics,
Heinrich-Pette-Institut für experimentelle Virologie und
Immunologie an der Universität Hamburg, Hamburg, Germany.
Hematopoiesis is tightly controlled by a family of cytokines that
signal through a related set of receptors. The pleiotropic and
overlapping response of a cell to different cytokines is reflected in
the number and complex pattern of activated signal transducers. Of
special interest is STAT5, which is stimulated by a large and diverse
set of cytokines. In addition to the two highly homologous proteins,
STAT5A and STAT5B, encoded by duplicated genes, expression and
activation of a dominant-negative, carboxyl-truncated form has also
been described in early hematopoietic progenitors. We show here that a
protease expressed in early hematopoietic cells cleaves the  forms
of STAT5A/5B (p96/p94) to generate carboxyl-truncated  forms
(p80/p77). Inhibition studies assigned this protease to the serine
class of endopeptidases. Cell fractionation experiments showed that the
protease is associated with the nucleus in a constitutively activated
form and does not require an activated STAT5 substrate. The ability of
a protease to modulate the specificity of an activated transcription
factor is unprecedented and underlines the importance of proteases in
regulation of cell functions.
Blood, Vol. 91 No. 6 (March 15), 1998:
pp. 1901-1908
© 1998 by The American Society of Hematology.
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