Differential ability of SOCS proteins to regulate IL-6 and CSF-1 induced macrophage differentiation.
M1/WT4 cells, derived from the murine myeloid leukemic M1 cells by over-expression of the receptor for CSF-1, were transfected with expression vectors encoding SOCS-1, SOCS-2, SOCS-3 or Cis-1. The differentiation response to CSF-1 and IL-6 was analyzed in the resulting cell lines. Myeloid differentiation in response to CSF-1 was not affected by any of the SOCS proteins, whereas the IL-6-mediated differentiation was inhibited by SOCS-1 and SOCS-3 and slightly delayed by SOCS-2 expression. In M1/WT4 cells IL-6 causes strong tyrosine phosphorylation of STAT3, whereas the response to CSF-1 is weaker. The expression of the SOCS proteins had no effect on CSF-1 mediated STAT3 tyrosine phosphorylation; however, SOCS-1 and SOCS-3 reduced the tyrosine phosphorylation of STAT3 in response to IL-6 but did not abolish it. It appears, therefore, that SOCS-1, -2 and -3 and Cis-1 do not inhibit tyrosine kinase activity involved in CSF-1 mediated cell differentiation, whereas SOCS-1 and -3 are inhibiting kinase activity required for IL-6-mediated differentiation.
Novak
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Department of Surgery, University of Melbourne, Royal Melbourne Hospital, Parkville, Vic., Australia. u.novak@medicine.unimelb.edu.au
Marks
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Nicholson
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Hilton
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Paradiso
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D000209:Acute-Phase Proteins / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D015850:Interleukin-6 / Q000494:pharmacology*; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology*; D051379:Mice; D011506:Proteins / Q000494:pharmacology*; D012097:Repressor Proteins; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014407:Tumor Cells, Cultured; D018909:src Homology Domains / Q000187:drug effects
D000209:Acute-Phase Proteins; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D011506:Proteins; D012097:Repressor Proteins; D050796:STAT3 Transcription Factor; C491409:Socs2 protein, mouse; C491411:Socs3 protein, mouse; C494087:Stat3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D016173:Macrophage Colony-Stimulating Factor