Functional expression of the macrophage colony-stimulating factor receptor in human THP-1 monocytic leukemia cells.

Abstract

Macrophage colony-stimulating factor (M-CSF) is required for the proliferation, differentiation, and activation of monocytes. High-affinity receptors for M-CSF are encoded by the c-fms proto-oncogene. In the present study, we show that c-fms transcripts are detectable in human THP-1 myeloid leukemia cells. Furthermore, radiolabeled 125I-M-CSF is rapidly internalized into THP-1 cells and then degraded intracellularly. The results also show that treatment of THP-1 cells with M-CSF is associated with the activation of protein kinase C (PKC) and the induction of tumor necrosis factor (TNF) gene expression. TNF transcript levels were low to undetectable in uninduced THP-1 cells, reached maximal levels by 1 hour of exposure to M-CSF, and returned to those of control cells by 24 hours. Transcriptional run-on analysis showed that a low level of TNF transcription is detectable in untreated THP-1 cells, and M-CSF treatment increased the rate of TNF transcription. Pretreatment of THP-1 cells with pertussis toxin inhibited the increase in PKC activity but not the induction of TNF transcripts by M-CSF. Moreover, exposure of THP-1 cells to inhibitors of protein kinase activity blocked the increase in TNF messenger RNA. These findings suggest that at least two M-CSF-mediated signaling pathways exist in THP-1 cells and that the induction of TNF may be regulated by a protein kinase-dependent mechanism distinct from PKC.

• Authors: R Datta, K Imamura, S J Goldman, A C Dianoux, D W Kufe, M L Sherman
• Journal: Blood (Blood) Vol. 79 Issue 4 Pg. 904-12 (Feb 15 1992) ISSN: 0006-4971 [Print] United States
• PMID: 1531307 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Isoquinolines
• MAS1 protein, human
• Piperazines
• Protein Kinase Inhibitors
• Proto-Oncogene Mas
• RNA, Messenger
• Tumor Necrosis Factor-alpha
• Virulence Factors, Bordetella
• Biotin
• Macrophage Colony-Stimulating Factor
• 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
• Pertussis Toxin
• Receptor, Macrophage Colony-Stimulating Factor
• Protein Kinase C

Topics

• 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
• Biotin
• Enzyme Activation
• Flow Cytometry
• Gene Expression
• Gene Expression Regulation (drug effects)
• Humans
• Isoquinolines (pharmacology)
• Leukemia, Myelomonocytic, Acute (metabolism)
• Macrophage Colony-Stimulating Factor (metabolism, pharmacology)
• Pertussis Toxin
• Piperazines (pharmacology)
• Protein Kinase C (metabolism)
• Protein Kinase Inhibitors
• Proto-Oncogene Mas
• RNA, Messenger (metabolism)
• Receptor, Macrophage Colony-Stimulating Factor (genetics)
• Transcription, Genetic
• Tumor Cells, Cultured
• Tumor Necrosis Factor-alpha (genetics)
• Virulence Factors, Bordetella (pharmacology)