scholarly journals Association of p72 tyrosine kinase with Stat factors and its activation by interleukin-3, interleukin-6, and granulocyte colony-stimulating factor

Blood ◽  
1994 ◽  
Vol 83 (12) ◽  
pp. 3457-3461 ◽  
Author(s):  
T Matsuda ◽  
T Hirano
Keyword(s):  
Tyrosine Kinase ◽  
Kinase Activity ◽  
Signal Transduction Pathway ◽  
Oncostatin M ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Tyrosine Kinase Activity ◽  
Interleukin 3 ◽  
Hematopoietic Lineage ◽  
Stimulating Factor

Hematopoietic cytokines, including interleukin-3 (IL-3), IL-6, and granulocyte colony-stimulating factor (G-CSF), induce the proliferation, differentiation, and activation of hematopoietic lineage cells. These cytokines activate the Jak/Stat-mediated signal transduction pathway that is important in the biologic activities of these cytokines. In this study, we showed that hematopoietic cytokines, such as IL-3, IL-6, and G-CSF, all induced tyrosine-phosphorylation of Stat family proteins and Stat-associated 150-kD and 72-kD molecules in hematopoietic lineage cell lines. Furthermore, we showed that the 72-kD molecule had tyrosine kinase activity. The tyrosine kinase activity of the 72-kD molecule was enhanced by the stimulation through an IL-6 signal transducer, gp130, that was shared among the receptors for the IL-6-related cytokine subfamily, such as leukemia inhibitory factor, oncostatin M, IL-11, and ciliary neurotrophic factor. Because 72-kD tyrosine kinase was distinct from Syk, Tec, and Btk and coimmunoprecipitated with anti-Stat antiserum, we termed it Stat- associated 72-kD tyrosine kinase (p72sak). p72sak may directly activate Stat family proteins or other signal transducing molecules for IL-3, G- CSF, and the IL-6-related cytokine subfamily.

scholarly journals Association of p72 tyrosine kinase with Stat factors and its activation by interleukin-3, interleukin-6, and granulocyte colony-stimulating factor

Blood ◽  
1994 ◽  
Vol 83 (12) ◽  
pp. 3457-3461 ◽  
Author(s):  
T Matsuda ◽  
T Hirano
Keyword(s):  
Tyrosine Kinase ◽  
Kinase Activity ◽  
Signal Transduction Pathway ◽  
Oncostatin M ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Tyrosine Kinase Activity ◽  
Interleukin 3 ◽  
Hematopoietic Lineage ◽  
Stimulating Factor

Abstract Hematopoietic cytokines, including interleukin-3 (IL-3), IL-6, and granulocyte colony-stimulating factor (G-CSF), induce the proliferation, differentiation, and activation of hematopoietic lineage cells. These cytokines activate the Jak/Stat-mediated signal transduction pathway that is important in the biologic activities of these cytokines. In this study, we showed that hematopoietic cytokines, such as IL-3, IL-6, and G-CSF, all induced tyrosine-phosphorylation of Stat family proteins and Stat-associated 150-kD and 72-kD molecules in hematopoietic lineage cell lines. Furthermore, we showed that the 72-kD molecule had tyrosine kinase activity. The tyrosine kinase activity of the 72-kD molecule was enhanced by the stimulation through an IL-6 signal transducer, gp130, that was shared among the receptors for the IL-6-related cytokine subfamily, such as leukemia inhibitory factor, oncostatin M, IL-11, and ciliary neurotrophic factor. Because 72-kD tyrosine kinase was distinct from Syk, Tec, and Btk and coimmunoprecipitated with anti-Stat antiserum, we termed it Stat- associated 72-kD tyrosine kinase (p72sak). p72sak may directly activate Stat family proteins or other signal transducing molecules for IL-3, G- CSF, and the IL-6-related cytokine subfamily.

Tyrosine 569 in the c-Fms juxtamembrane domain is essential for kinase activity and macrophage colony-stimulating factor-dependent internalization

1994 ◽  
Vol 14 (7) ◽  
pp. 4843-4854
Author(s):  
G M Myles ◽  
C S Brandt ◽  
K Carlberg ◽  
L R Rohrschneider
Keyword(s):  
Amino Acid ◽  
Tyrosine Kinase ◽  
Kinase Activity ◽  
Colony Stimulating Factor ◽  
Tyrosine Kinase Activity ◽  
Recognition Sequence ◽  
Juxtamembrane Region ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

The receptor (Fms) for macrophage colony-stimulating factor (M-CSF) is a member of the tyrosine kinase class of growth factor receptors. It maintains survival, stimulates growth, and drives differentiation of the macrophage lineage of hematopoietic cells. Fms accumulates on the cell surface and becomes activated for signal transduction after M-CSF binding and is then internalized via endocytosis for eventual degradation in lysosomes. We have investigated the mechanism of endocytosis as part of the overall signaling process of this receptor and have identified an amino acid segment near the cytoplasmic juxtamembrane region surrounding tyrosine 569 that is important for internalization. Mutation of tyrosine 569 to alanine (Y569A) eliminates ligand-induced rapid endocytosis of receptor molecules. The mutant Fms Y569A also lacks tyrosine kinase activity; however, tyrosine kinase activity is not essential for endocytosis because the kinase inactive receptor Fms K614A does undergo ligand-induced endocytosis, albeit at a reduced rate. Mutation of tyrosine 569 to phenylalanine had no effect on the M-CSF-induced endocytosis of Fms, and a four-amino-acid sequence containing Y-569 could support endocytosis when transferred into the cytoplasmic juxtamembrane region of a glycophorin A construct. These results indicate that tyrosine 569 within the juxtamembrane region of Fms is part of a signal recognition sequence for endocytosis that does not require tyrosine phosphorylation at this site and that this domain also influences the kinase activity of the receptor. These results are consistent with a ligand-dependent step in recognition of the potential cryptic internalization signal.

scholarly journals Tyrosine 569 in the c-Fms juxtamembrane domain is essential for kinase activity and macrophage colony-stimulating factor-dependent internalization.

1994 ◽  
Vol 14 (7) ◽  
pp. 4843-4854 ◽  
Author(s):  
G M Myles ◽  
C S Brandt ◽  
K Carlberg ◽  
L R Rohrschneider
Keyword(s):  
Amino Acid ◽  
Tyrosine Kinase ◽  
Kinase Activity ◽  
Colony Stimulating Factor ◽  
Tyrosine Kinase Activity ◽  
Recognition Sequence ◽  
Juxtamembrane Region ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

The receptor (Fms) for macrophage colony-stimulating factor (M-CSF) is a member of the tyrosine kinase class of growth factor receptors. It maintains survival, stimulates growth, and drives differentiation of the macrophage lineage of hematopoietic cells. Fms accumulates on the cell surface and becomes activated for signal transduction after M-CSF binding and is then internalized via endocytosis for eventual degradation in lysosomes. We have investigated the mechanism of endocytosis as part of the overall signaling process of this receptor and have identified an amino acid segment near the cytoplasmic juxtamembrane region surrounding tyrosine 569 that is important for internalization. Mutation of tyrosine 569 to alanine (Y569A) eliminates ligand-induced rapid endocytosis of receptor molecules. The mutant Fms Y569A also lacks tyrosine kinase activity; however, tyrosine kinase activity is not essential for endocytosis because the kinase inactive receptor Fms K614A does undergo ligand-induced endocytosis, albeit at a reduced rate. Mutation of tyrosine 569 to phenylalanine had no effect on the M-CSF-induced endocytosis of Fms, and a four-amino-acid sequence containing Y-569 could support endocytosis when transferred into the cytoplasmic juxtamembrane region of a glycophorin A construct. These results indicate that tyrosine 569 within the juxtamembrane region of Fms is part of a signal recognition sequence for endocytosis that does not require tyrosine phosphorylation at this site and that this domain also influences the kinase activity of the receptor. These results are consistent with a ligand-dependent step in recognition of the potential cryptic internalization signal.

scholarly journals Human colony-stimulating factor 1 (CSF-1) receptor confers CSF-1 responsiveness to interleukin-3-dependent 32DC13 mouse myeloid cells and abrogates differentiation in response to granulocyte CSF

Blood ◽  
1990 ◽  
Vol 75 (9) ◽  
pp. 1780-1787 ◽  
Author(s):  
J Kato ◽  
CJ Sherr
Keyword(s):  
Tyrosine Phosphorylation ◽  
Functional Properties ◽  
Phorbol Esters ◽  
Mononuclear Phagocyte ◽  
Nonspecific Esterase ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Interleukin 3 ◽  
Substrate Phosphorylation ◽  
Stimulating Factor

Abstract Interleukin-3 (IL-3)-dependent mouse myeloid 32DC13 cells differentiate to neutrophils in response to granulocyte colony-stimulating factor (G- CSF). Introduction of the human c-fms gene, which encodes the receptor for CSF-1, into 32DC13 cells gave rise to variants that were able to proliferate in medium containing either murine IL-3 or human recombinant CSF-1, but were unable to differentiate to granulocytes in response to G-CSF. Unlike parental 32CD13 cells, CSF-1-responsive derivatives expressed nonspecific esterase when grown in CSF-1, but did not exhibit many other morphologic, immunologic, or functional properties of mononuclear phagocyte differentiation, or express murine CSF-1 receptors. Accelerated turnover of the human CSF-1 receptor was observed in response to CSF-1 and phorbol esters, but not after stimulation with IL-3 or bacterial lipopolysaccharide. Although both CSF-1 and IL-3 induced tyrosine phosphorylation of heterologous substrates in the dually responsive cells, differences in the patterns of substrate phosphorylation were observed in response to the two hematopoietins. We conclude that expression of the human CSF-1 receptor in 32DC13 cells not only induces CSF-1 responsiveness, but alters its phenotype in a way that prohibits granulocyte differentiation.

scholarly journals Target cells for granulocyte colony-stimulating factor, interleukin-3, and interleukin-5 in differentiation pathways of neutrophils and eosinophils

Blood ◽  
1990 ◽  
Vol 76 (10) ◽  
pp. 1956-1961 ◽  
Author(s):  
H Ema ◽  
T Suda ◽  
K Nagayoshi ◽  
Y Miura ◽  
CI Civin ◽  
...  
Keyword(s):  
Bone Marrow Cells ◽  
Early Stage ◽  
Target Cells ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Interleukin 3 ◽  
Cd34 Antigen ◽  
Cd34 Cells ◽  
Stimulating Factor

Abstract To study the relationship between hematopoietic factors and their responsive hematopoietic progenitors in the differentiation process, both purified factors and enriched progenitors are required. We isolated total CD34+ cells, CD34+,CD33+ cells, and CD34+,CD33- cells individually from normal human bone marrow cells by fluorescence- activated cell sorter (FACS), and examined the effects of granulocyte colony-stimulating factor (G-CSF), interleukin-3 (IL-3), and IL-5 on in vitro colony formation of these cells. CD34+,CD33+ cells formed granulocyte colonies in the presence of G-CSF. Both CD34+,CD33+ cells and CD34+,CD33- cells formed granulocyte/macrophage colonies in the presence of IL-3. Eosinophil (Eo) colonies were only formed by CD34+,CD33- cells in response to IL-3, but scarcely formed by CD34+ cells in the presence of IL-5. We performed the two-step cultures consisting of the primary liquid culture for 6 days and the secondary methylcellulose culture, and serially examined changes in phenotypes of ,he cells cultured in the primary culture. CD34-,CD33+ cells derived from CD34+,CD33+ cells by preincubation with G-CSF or IL-3 formed Eo colonies in the presence of IL-5 but not IL-3. CD34-,CD33+ cells derived from CD34+,CD33- cells by preincubation with IL-3 also formed Eo colonies by support of IL-5 as well as IL-3. Both CD34+ cells gradually lost the CD34 antigen by day 6 of incubation with G-CSF or IL- 3. Loss of this antigen was well-correlated with acquisition of susceptibility to IL-5. It was concluded that G-CSF supported the neutrophil differentiation of committed colony-forming cells, IL-3 supported that of both committed and multipotent colony-forming cells. G-CSF and IL-3 also supported the early stage of E. differentiation; IL- 5 supported the late stage of that.

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

Blood ◽  
1994 ◽  
Vol 84 (6) ◽  
pp. 1760-1764 ◽  
Author(s):  
SS Tian ◽  
P Lamb ◽  
HM Seidel ◽  
RB Stein ◽  
J Rosen
Keyword(s):  
Dna Binding ◽  
Tyrosine Phosphorylation ◽  
Tyrosine Kinases ◽  
Signal Transduction Pathway ◽  
Binding Activity ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Dna Binding Activity ◽  
Dna Binding Complexes ◽  
Stimulating Factor

Abstract 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.

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