Association of Cbl with Fms and p85 in response to macrophage colony-stimulating factor.
Tyrosine phosphorylation of Cbl and its association with signal-transducing molecules in response to macrophage colony-stimulating factor (M-CSF) were analyzed by using cell lines which express the wild-type and a mutant M-CSF receptor, Fms. We found that in a clone, F723 TF-1 cells expressing mutant Fms in which tyrosine 723 had been substituted with phenylalanine, the M-CSF stimulation-dependent association between Cbl and Fms was markedly impaired. However, phosphorylation of Cbl and its association with the p85 subunit of phosphatidylinositol 3-kinase were induced in these mutant cells as seen in the wild-type fms transfectant. These results suggest that phosphorylation of tyrosine 723 is particularly important for the recruitment of Cbl to the M-CSF receptor, but is not required for the phosphorylation and binding of Cbl to signal-transducing molecules such as p85.
Ota
J
J
Biochemical Research Laboratory, Morinaga Milk Industry, Higashihara 5-1-83, Zama, Kanagawa, Japan.
Sato
K
K
Kimura
F
F
Wakimoto
N
N
Nakamura
Y
Y
Nagata
N
N
Suzu
S
S
Yamada
M
M
Shimamura
S
S
Motoyoshi
K
K
D000581:Amidohydrolases; D019943:Amino Acid Substitution; D000626:Aminopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D002999:Clone Cells; D017931:DNA Primers / Q000235:genetics; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D016297:Mutagenesis, Site-Directed; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D050721:Proto-Oncogene Proteins c-cbl; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013379:Substrate Specificity; D014162:Transfection; D014443:Tyrosine / Q000737:chemistry; D044767:Ubiquitin-Protein Ligases
D017931:DNA Primers; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D014443:Tyrosine; D016173:Macrophage Colony-Stimulating Factor; D050721:Proto-Oncogene Proteins c-cbl; D044767:Ubiquitin-Protein Ligases; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; D016186:Receptor, Macrophage Colony-Stimulating Factor; D000626:Aminopeptidases; D000581:Amidohydrolases; C084507:peptide deformylase; C067419:CBL protein, human; C493849:Cbl protein, mouse