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Biotech / Medical : Ligand (LGND) Breakout!
LGND 189.55+3.5%Dec 12 9:30 AM EST

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To: Flagrante Delictu who wrote (13065)1/7/1998 3:35:00 PM
From: Henry Niman   of 32384
 
Here's one on phosphorylation of STATs:

Blood 1994 Sep 15;84(6):1760-1764

Rapid activation of the STAT3 transcription factor by
granulocyte colony-stimulating factor.

Tian SS, Lamb P, Seidel HM, Stein RB, Rosen J

Granulocyte colony-stimulating factor (G-CSF) is a glycoprotein that stimulates proliferation and
differentiation of progenitor cells of neutrophils by signaling through its receptor (G-CSFR).
Although the G-CSFR belongs to the cytokine receptor superfamily, which lacks an intracellular
kinase domain, G-CSF-induced tyrosine phosphorylation of cellular proteins is critical for its
biologic activities. We report here that JAK1 and JAK2 tyrosine kinases are tyrosine
phosphorylated in response to G-CSF induction. We also demonstrate that the DNA-binding
protein STAT3 (also called the acute-phase response factor [APRF], activated by interleukin-6) is
an early target of G-CSF-induced tyrosine phosphorylation. G-CSF induces two DNA-binding
complexes; the major complex contains tyrosine phosphorylated STAT3 protein and the minor
complex appears to be a heterodimer of the STAT1 (previously p91, a component of DNA-binding
complexes activated by interferons) and STAT3 proteins. Antiphosphotyrosine antibody interferes
with the DNA binding activity of activated STAT3, indicating that tyrosine phosphorylation of
STAT3 is important for the DNA binding activity. These results identify a signal transduction
pathway activated in response to G-CSF and provide a mechanism for the rapid modulation of gene
expression by G-CSF.

PMID: 7521688, UI: 94362223
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