A soluble fibroblast growth factor receptor is released from HL-60 promyelocytic leukemia cells: implications for paracrine growth control
| Autor: | M. Shen, David J. Hill, G. H. Fong, J. F. Wang |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Recombinant Fusion Proteins
Clinical Biochemistry Blotting Western HL-60 Cells Biology Culture Media Serum-Free Paracrine signalling Endocrinology Cell surface receptor Paracrine Communication Tumor Cells Cultured Humans Receptor Fibroblast Growth Factor Type 1 Fibroblast growth factor receptor 2 Reverse Transcriptase Polymerase Chain Reaction Fibroblast growth factor receptor 1 Receptor Protein-Tyrosine Kinases Cell Biology Fibroblast growth factor receptor 4 DNA Neoplasm Fibroblast growth factor receptor 3 Fusion protein Molecular biology Receptors Fibroblast Growth Factor Peptide Fragments Protein Structure Tertiary stomatognathic diseases Solubility Fibroblast growth factor receptor Fibroblast Growth Factor 2 Cell Division Thymidine |
| Zdroj: | Growth factors (Chur, Switzerland). 17(3) |
| ISSN: | 0897-7194 |
| Popis: | The biological activities of fibroblast growth factors (FGF) are mediated by specific cell membrane receptors (FGFR), which have three immunoglobulin-like IgG domains in the extracellular region. The carboxy-terminal segment of the third IgG domain of FGFR1 could be encoded by different exons, designated IIIa, IIIb, or IIIc. While exons IIIb or IIIc encode receptor forms with both intracellular and extracellular domains, the FGF receptor becomes potentially a secreted form lacking the intracellular domain and the transmembrane region when exon IIIa is expressed. Using reverse transcription polymerase chain reaction, we have found that mRNAs encoding the nucleotide sequences of FGFR1-IIIa and FGFR1-IIIc are expressed in HL-60 cells. FGFR1-IIIa fragment was synthesized by a glutathione S-transferase gene fusion system. The purified 33 kDa FGFR1-IIIa fragment fusion protein could bind [125I]-labelled FGF-2 in Western ligand blot analysis. Three species of proteins with the molecular weights of 82, 60, and 50 kDa were identified in serum-free, conditioned medium from HL-60 cells by Western blot using an antiserum against purified FGFR1-IIIa fragment fusion protein. Exposure to FGF-2 caused an increase in [3H]-thymidine incorporation into DNA of HL-60 cells and increased cell proliferation, but the addition of FGFR1-IIIa fragment fusion protein inhibited FGF-2-stimulated DNA synthesis and caused a dose-dependent inhibition of FGF-2-stimulated cell proliferation. The effects on DNA synthesis were partly reversed by antibody against the FGFR1-IIIa fragment. These results indicate that both cell membrane spanning and secreted FGF receptors are expressed in HL-60 cells, and that the actions of FGFs as paracrine growth factors could be modulated by secreted FGF receptor forms. |
| Databáze: | OpenAIRE |
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