Agonist-specifictyrosine phosphorylationof CbI in human neutrophils

The effects of soluble and particulate ago- fists on the tyrosine phosphorylation levels of the proto-oncogene Cbl in human neutrophils were exam- ined. Experimental conditions allowing the mainte- nance of Cbl as well as of its tyrosine phosphorylation status were first established. Their use allowed us to observe that Cbl was tyrosine phosphorylated in response to some (Fc'yRII ligation, opsonized bacteria and zymosan, granulocyte-macrophage colony-stimulating factor, monosodium urate, and calcium pyrophosphate microcrystals), but not all (fMet-Leu-Phe, interleukin- 8) neutrophil agonists. Cbl was also shown to account for a varying proportion of the 120-kDa phosphopro- tein(s) observed in response to the above stimuli. These data establish that Cbl is present in human neu- trophils and that its level of tyrosine phosphorylation is modulated by some of these cells' agonists, and in particular by phagocytic particles. Furthermore, the signaling pathways activated by chemotactic factors and the other neutrophil stimuli tested in this investi- gation diverge at or downstream from the tyrosine phosphorylation of Cbl. J. Leukoc. Biol. 62: 901-910; 1997.