scholarly journals pH Dependence of structural stability of interleukin-2 and granulocyte colony-stimulating factor

2003 ◽  
Vol 12 (5) ◽  
pp. 1030-1038 ◽  
Author(s):  
Margaret Speed Ricci ◽  
Casim A. Sarkar ◽  
Eric M. Fallon ◽  
Douglas A. Lauffenburger ◽  
David N. Brems
Keyword(s):  
Structural Stability ◽  
Ph Dependence ◽  
Interleukin 2 ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Stimulating Factor

DOWNREGULATION OF BOTH INTERLEUKIN-12 AND INTERLEUKIN-2 IN HEART ALLOGRAFTS BY PRETRANSPLANT HOST TREATMENT WITH GRANULOCYTE COLONY-STIMULATING FACTOR AND TACROLIMUS

Cytokine ◽  
2002 ◽  
Vol 18 (3) ◽  
pp. 164-167 ◽  
Author(s):  
Hiroyuki Egi ◽  
Keisuke Hayamizu ◽  
Teruhiko Kitayama ◽  
Ichiro Ohmori ◽  
Masazumi Okajima ◽  
...  
Keyword(s):  
Interleukin 2 ◽  
Interleukin 12 ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Stimulating Factor

A potential therapeutic role for small nonpeptidyl compounds that mimic human granulocyte colony-stimulating factor

Blood ◽  
2004 ◽  
Vol 103 (3) ◽  
pp. 836-842 ◽  
Author(s):  
Kouji Kusano ◽  
Shinji Ebara ◽  
Koichi Tachibana ◽  
Tadahiro Nishimura ◽  
Susumu Sato ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Interleukin 2 ◽  
Immune Defense ◽  
Mitogen Activated Protein Kinase ◽  
Human Neutrophils ◽  
Blood Neutrophil ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Stimulating Factor

AbstractGranulocyte colony-stimulating factor (G-CSF) stimulates the proliferation of bone marrow granulocytic progenitor cells and promotes their differentiation into granulocytes. G-CSF is therefore an important component of immune defense against pathogenic microorganisms: recombinant human G-CSF (rhG-CSF) is used to treat patients with a variety of neutropenias. In the present study, we screened approximately 10 000 small nonpeptidyl compounds and found 3 small compounds that mimic G-CSF in several in vitro and in vivo assays. These compounds induced G-CSF–dependent proliferation, but had no effect on interleukin-3–dependent, interleukin-2–dependent, interleukin-10–dependent, thrombopoietin (TPO)–dependent, or erythropoietin (EPO)–dependent proliferation. Each compound induced the phosphorylation of signal transducers and activators of transcription–3 (STAT3) and mitogen-activated protein kinase (MAPK) in a G-CSF–dependent cell line and in human neutrophils. In addition, these compounds induced hematopoietic colony formation from primary rat bone marrow cells in vitro. When subcutaneously injected into normal rats, they caused an increase in peripheral blood neutrophil counts. Furthermore, when they were administered to cyclophosphamide-induced neutropenic rats, blood neutrophil levels increased and remained elevated up to day 8. We therefore suggest that these small nonpeptidyl compounds mimic the activity of G-CSF and may be useful in the treatment of neutropenic patients.

scholarly journals Identification of a signal-transduction pathway shared by haematopoietic growth factors with diverse biological specificity

1987 ◽  
Vol 244 (3) ◽  
pp. 683-691 ◽  
Author(s):  
S W Evans ◽  
D Rennick ◽  
W L Farrar
Keyword(s):  
Signal Transduction ◽  
Protein Kinase C ◽  
Growth Factors ◽  
Interleukin 2 ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Kinase C ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

The haematopoietic growth factors multi-colony-stimulating factor, granulocyte/macrophage colony-stimulating factor, granulocyte colony-stimulating factor and interleukin 2 specifically control the production and proliferation of distinct leucocyte series. Each growth factor acts on a unique surface receptor associated with an appropriate signal-transduction apparatus. In this report we identify a 68 kDa substrate which is phosphorylated after stimulation of different cell types with multi-colony-stimulating factor, granulocyte colony-stimulating factor and interleukin 2. The 68 kDa substrate is also phosphorylated in each cell line stimulated with synthetic diacylglycerol, a direct activator of protein kinase C. Interestingly, granulocyte/macrophage colony-stimulating factor does not induce phosphorylation of the 68 kDa molecule. The 68 kDa molecule that is phosphorylated after stimulation with each ligand yielded similar peptide maps after chymotryptic digestion; furthermore, the substrate was always phosphorylated on threonine residues. Phosphorylation of the same residues in the 68 kDa substrate suggests that activation of protein kinase C is one common signal-transduction event associated with the action of multi-colony-stimulating factor, granulocyte colony-stimulating factor and interleukin 2.

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