Extracellular signal-regulated kinase and p38 mitogen-activated protein kinase pathways cooperate in mediating cytokine-induced proliferation of a leukemic cell line

Autor: PD Doshi, SP Srinivasa
Rok vydání: 2001
Předmět:
MAPK/ERK pathway
Cancer Research
MAP Kinase Signaling System
Recombinant Fusion Proteins
Blotting
Western
Biology
Mitogen-activated protein kinase kinase
p38 Mitogen-Activated Protein Kinases
MAP2K7
Colony-Stimulating Factors
Computer Systems
Cyclins
Granulocyte Colony-Stimulating Factor
Tumor Cells
Cultured
Humans
ASK1
Phosphorylation
MAPK14
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
MAP kinase kinase kinase
Gene Expression Regulation
Leukemic
Reverse Transcriptase Polymerase Chain Reaction
Cyclin-dependent kinase 2
Cell Cycle
Membrane Proteins
Drug Synergism
Hematology
Precipitin Tests
Recombinant Proteins
Cell biology
Neoplasm Proteins
Oncology
Leukemia
Monocytic
Acute
Receptors
Granulocyte Colony-Stimulating Factor
Cancer research
biology.protein
Cyclin-dependent kinase 9
Mitogen-Activated Protein Kinases
Protein Processing
Post-Translational
Cell Division
Transcription Factors
Zdroj: Leukemia. 16(2)
ISSN: 0887-6924
Popis: Granulocyte colony-stimulating factor (G-CSF) and fetal liver tyrosine kinase-3 (Flt3) ligand (FL) act in synergy to induce expansion and mobilization of hematopoietic progenitor cells. Regulation of mitogen activated protein (MAP) kinase pathways and gene transcription, induced by these cytokines were examined using the OCI-AML5 cell line. For this purpose, FL and G-CSF were used either alone, or in combination as the co-addition of FL and G-CSF (FL+G-CSF), or a chimeric molecule, progenipoietin-1 (ProGP-1). Both G-CSF and FL induced phosphorylation of extracellular signal-regulated kinases (ERKs) while p38 mitogen activated protein (MAP) kinase was phosphorylated only in response to G-CSF but not FL. Studies using specific kinase inhibitors suggested that both ERK and p38 MAP kinase pathways were required for the optimal cell proliferation in response to both G-CSF and FL. The magnitude of activation of the ERK pathway and induction of genes involved in cell cycle progression by G-CSF and FL exhibited a strong correlation with the degree of cell proliferation. These data suggest that OCI-AML5 cells proliferate at least in part, due to the activation of both ERK and p38 MAP kinase pathways in response to G-CSF and FL. This study represents the first report of the specific cell cycle genes induced by FL.
Databáze: OpenAIRE
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