Protein tyrosine kinases in granulocyte colony stimulating factor receptor signal transduction, myeloid cell proliferation, and neutrophil activation Journal Article
| Authors: | Deshpande, R. V.; Peterson, R. H. F.; Moore, M. A. S. |
| Article Title: | Protein tyrosine kinases in granulocyte colony stimulating factor receptor signal transduction, myeloid cell proliferation, and neutrophil activation |
| Abstract: | Granulocyte colony-stimulating factor (G-CSF) plays an important role in the growth and maturation of granulocytic precursor cells. Although the interaction between G-CSF and its receptor (G-CSF-R) is an obligatory event during proliferation and differentiation of myeloid cells, the signal transduction mechanisms leading to these effects are not completely known. We investigated the kinetics of protein tyrosine kinase (PTK) activation in G-CSF-R signal transduction in myeloid leukemic cell lines and peripheral blood neutrophils. G-CSF treatment of myeloid cell-lines (HL-60, KG-1, NFS-60) and neutrophils resulted in a rapid increase in PTK activity. This induction was inhibited by an anti-G-CSF monoclonal antibody and various PTK-specific inhibitors. PTK activity was important for proliferation of myeloid cells; its inhibition resulted in decreased proliferation and clonogenicity of these cells. PTK-induction was not involved in G-CSF-R expression, internalization or recycling, but was partially responsible for up-regulation of CD11b expression on neutrophils. In contrast to neutrophilic cell-lines, the myelo-monocytic cell lines (U-937, WEHI-3B) showed no change in PTK levels in response to G-CSF. The results indicate that the G-CSF-R-mediated PTK up-regulation may be a neutrophil-lineage-restricted signal, and that PTK may play an important role in the proliferation of neutrophil-precursors and functional activation of mature neutrophils. |
| Keywords: | signal transduction; controlled study; unclassified drug; human cell; nonhuman; flow cytometry; cell proliferation; animal cell; mouse; animals; mice; cell division; cell line; cell differentiation; enzyme activity; protein tyrosine kinase; animalia; stem cell; monoclonal antibody; protein tyrosine kinase inhibitor; drug antagonism; neutrophil; enzyme inhibitors; granulocyte colony stimulating factor receptor; neutrophils; protein-tyrosine kinases; bone marrow cell; monocytes; recombinant granulocyte colony stimulating factor; macrophage; macrophages; clonogenic assay; colony-forming units assay; cell activation; granulocyte colony-stimulating factor; recombinant granulocyte macrophage colony stimulating factor; leukemia cell line; enzyme induction; genistein; daidzein; cellular proliferation; hl-60 cells; cell strain hl 60; receptors, granulocyte colony-stimulating factor; growth factors; lavendustin a; humans; human; article; macrophage-1 antigen; cell signalling; 2,5 dihydroxycinnamic acid methyl ester; granulocyte colony stimulating factor antibody; lavendustin b; tyrphostin a1; tyrphostin a25 |
| Journal Title: | Life Sciences |
| Volume: | 60 |
| Issue: | 9 |
| ISSN: | 0024-3205 |
| Publisher: | Elsevier Inc. |
| Date Published: | 1997-01-24 |
| Start Page: | 587 |
| End Page: | 604 |
| Language: | English |
| DOI: | 10.1016/s0024-3205(96)00697-2 |
| PUBMED: | 9048962 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 17 March 2017 -- Source: Scopus |
