C‐kit mutations and PKC crosstalks: PKC translocates to nucleous only in cells HMC560,816

Abstract

The human mast cell lines HMC-1(560) and HMC-1(560,816) were used to study histamine release, Ca(2+) signaling and protein kinase C (PKC) localization and expression, with phorbol 12-myristate 13-acetate (PMA). Both sublines carry activating mutations in the proto-oncogene of c-kit that cause autophosphorylation and permanent c-kit tyrosine kinase activation. Both have the Gly-560 → Val mutation but only the second carries the Asp-816 → Val mutation. In this study, it was observed that the stimulation of PKC has different effects in HMC-1(560) and HMC-1(560,816) and this would be related to the difference in activating mutations in both mast cell lines. PKC activation increases ionomycin-induced histamine release in HMC-1(560) . This article demonstrates an opposite histamine response in HMC-1(560,816) cells, even though classical PKCs are the family of isozymes responsible for this effect in both cellular lines. Furthermore, it can be observed that upon cell stimulation with PMA, primarily cytosolic PKC translocates to the nucleous in HMC-1(560,816) cells, but not in HMC-1(560) cell line.