Differential phosphorylation—Cause for defective internalization of aggregated IgG by chronic myeloid leukemic granulocytes?

Abstract

Granulocytes from the peripheral blood of patients with chronic myeloid leukemia (CML) are known to exhibit a defect in internalization of aggregated IgG relative to normal cells. As this aberration may arise due to defective transmembrane signalling, this study was undertaken to analyze alterations, if any, in protein phosphorylation between the two cell types. Normal and CML granulocytes were labeled with 32P-sodium orthophosphate and then stimulated with aggregated IgG. The phosphoproteins in the unstimulated and stimulated cells were analyzed by 2D-SDS-PAGE followed by autoradiography. The results show that there are five distinctly identifiable, reproducibly phosphorylated proteins referred to as Pp1-Pp5. In the unstimulated normal cells, Pp1 is less phosphorylated than Pp3, while in CML cells, Pp1 is more intense than Pp3. On stimulation of normal cells, with aggregated IgG, intensity of Pp1 increases while that of Pp3 decreases. In CML cells this response is reversed. We conclude that one of the causes for the defective internalization of IgG by CML granulocytes may probably be the observed differences in the phosphorylation of the proteins under study.