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Granulocyte-macrophage colony-stimulating factor preferentially activates
the 94-kD STAT5A and an 80-kD STAT5A isoform in human peripheral blood
monocytes
RL Rosen, KD Winestock, G Chen, X Liu, L Hennighausen and DS Finbloom
Division of Cytokine Biology, Food and Drug Administration, Bethesda, MD
20892-4555, USA.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) induces immediate
effects in monocytes by activation of the Janus kinase (JAK2) and STAT
transcription factor (STAT5) pathway. Recent studies have identified
homologues of STAT5, STAT5A, and STAT5B, as well as lower molecular weight
variants of STAT5. To define the activation of the STAT5 homologues and
lower molecular weight variant in human monocytes and monocytes
differentiated into macrophages by culture in macrophage- CSF (M-CSF), we
measured the GM-CSF induced tyrosine phosphorylation of STAT5A, STAT5B, and
any lower molecular weight STAT5 isoforms. Freshly isolated monocytes
expressed 94-kD STAT5A, 92-kD STAT5B, and an 80-kD STAT5A molecule. Whereas
94-kD STAT5A was clearly tyrosine phosphorylated and bound to the enhancer
element, the gamma response region (GRR), of the Fc gamma RI gene,
substantially less tyrosine phosphorylated STAT5B bound to the immobilized
GRR element. Macrophages lost their ability to express the 80-kD STAT5A
protein, but retained their ability to activate STAT5A. STAT5A-STAT5A
homodimers and STAT5A- STAT5B heterodimers formed in response to GM-CSF.
Therefore, activation of STAT5A predominates compared to STAT5B when
assayed by direct immunoprecipitation and by evaluation of bound STATs to
immobilized GRR. Selective activation of STAT5 homologues in addition to
generation of lower molecular isoforms may provide specificity and control
to genes expressed in response to cytokines such as GM-CSF.
Volume 88,
Issue 4,
pp. 1206-1214,
08/15/1996
Copyright © 1996 by The American Society of Hematology
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