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Carboxyl-Truncated STAT5β Is Generated by a Nucleus-Associated Serine Protease in Early Hematopoietic Progenitors

Authors :
Carol Stocking
Johann Meyer
Manfred Jücker
Wolfram Ostertag
Source :
Blood. 91:1901-1908
Publication Year :
1998
Publisher :
American Society of Hematology, 1998.

Abstract

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 α forms of STAT5A/5B (p96/p94) to generate carboxyl-truncated β 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.

Details

ISSN :
15280020 and 00064971
Volume :
91
Database :
OpenAIRE
Journal :
Blood
Accession number :
edsair.doi.dedup.....32ba16e8a34ec5922086184baa26d1ae
Full Text :
https://doi.org/10.1182/blood.v91.6.1901.1901_1901_1908