Carboxyl-truncated STAT5beta is generated by a nucleus-associated serine protease in early hematopoietic progenitors.
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 alpha forms of STAT5A/5B (p96/p94) to generate carboxyl-truncated beta 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.
Meyer
J
J
Department of Cell and Virus Genetics, Heinrich-Pette-Institut fur experimentelle Virologie und Immunologie an der Universitat Hamburg, Hamburg, Germany.
Jucker
M
M
Ostertag
W
W
Stocking
C
C
D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000201:enzymology*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D004789:Enzyme Activation; D006412:Hematopoietic Stem Cells / Q000201:enzymology*; D051379:Mice; D008894:Milk Proteins; D050799:STAT5 Transcription Factor; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism*
D004268:DNA-Binding Proteins; D008894:Milk Proteins; D050799:STAT5 Transcription Factor; D015842:Serine Proteinase Inhibitors; C494093:Stat5a protein, mouse; C494096:Stat5b protein, mouse; D015534:Trans-Activators