Requirement for Y706 of the murine (or Y708 of the human) CSF-1 receptor for STAT1 activation in response to CSF-1.
Using FDC-P1 derived cell lines which ectopically express either the wild type or mutant forms of the murine CSF-1 receptor in which individual tyrosine residues have been replaced with phenylalanine, we analysed the requirement for tyrosine residues of the receptor for the activation of STAT proteins in response to CSF-1. We found Y706 to be required for efficient activation of STAT1. The activation of STAT3 was not affected by the mutation of Y706 to phenylalanine. The addition of phosphopeptides spanning Y708 of the human CSF-1 receptor (identical with the sequence surrounding Y706 of the murine receptor) to electrophoretic mobility shift assays led to competition of the formation of STAT1 containing complexes, SIF-B and SIF-C with the DNA probe. These phosphopeptides did, however, not affect the formation of the STAT3 containing complex, SIF-A, with the probe. Replacement of Y807 with phenylalanine led to a complete block of activation of all STAT proteins in response to CSF-1, however, this phosphotyrosine does not appear to represent a STAT binding site of the receptor as a phosphopeptide spanning Y809 of the human CSF-1 receptor could not compete any STAT/DNA complex formation in electrophoretic mobility shift assays.
Novak
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U
University of Melbourne, Department of Medicine, Royal Melbourne Hospital, Parkville, Australia.
Nice
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E
Hamilton
J A
JA
Paradiso
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L
D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D051379:Mice; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases; D011506:Proteins / Q000378:metabolism; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000187:drug effects* / Q000378:metabolism; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D053634:TYK2 Kinase; D015534:Trans-Activators / Q000378:metabolism*
D004268:DNA-Binding Proteins; D011506:Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494080:Stat1 protein, mouse; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D016173:Macrophage Colony-Stimulating Factor; D011505:Protein-Tyrosine Kinases; D016186:Receptor, Macrophage Colony-Stimulating Factor; D053634:TYK2 Kinase; C070139:TYK2 protein, human; C499356:Tyk2 protein, mouse