AGONIST-SPECIFIC TYROSINE PHOSPHORYLATION OF CBL IN HUMAN NEUTROPHILS

The effects of soluble and particulate agonists on the tyrosine phosph orylation levels of the proto-oncogene Cbl in human neutrophils were e xamined, Experimental conditions allowing the maintenance of Cbl as we ll as of its tyrosine phosphorylation status were first established, T heir use allowed us to observe that Cbl was tyrosine phosphorylated in response to some (Fc gamma RII ligation, opsonized bacteria and zymos an, 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 phosphoprotein(s) observed In res ponse to the above stimuli, These data establish that Cbl is present i n human neutrophils and that its level of tyrosine phosphorylation is modulated by some of these cells' agonists, and in particular by phago cytic particles, Furthermore, the signaling pathways activated by chem otactic factors and the other neutrophil stimuli tested in this invest igation diverge at or downstream from the tyrosine phosphorylation of Cbl.