Protein kinase C isoforms in normal and chronic myeloid leukemic neutrophils. Distinct signal for PKC α by immunodetection on PVDF membrane, decreased expression of PKC α and increased expression of PKC δ in leukemic neutrophils

Abstract

Neutrophils from patients with Chronic Myeloid Leukemia (CML) exhibit defects in several functions. They also show altered phosphorylation–dephosphorylation patterns of several proteins on stimulation with phorbol myristate acetate—a direct activator of protein kinase C (PKC). Since PKC mediates several functions of the neutrophil, in this study we investigate the PKC isoform profile and subcellular distribution in normal and CML neutrophils in an attempt to elucidate their role in CML signalling. Our results show the presence of PKC α, βI, βII and δ in both the cell types. A distinct and clear signal was obtained for PKC α, the isoform reported to be absent or present in very low amounts in normal neutrophils. In addition, PKC α was present in significantly lower levels in CML neutrophils while the PKC δ isoform was found in significantly higher amounts in the CML cytosol as compared to that in normal cells. PKC α, βI, βII and δ isoforms could not be detected in the nucleus of unstimulated normal and CML neutrophils. The altered levels of PKC α and δ may be one of the causes for the defects in function exhibited by the leukemic cells.