Cross-talks between c-Kit and PKC isoforms in HMC-1(560) and HMC-1(560,816) cells. Different role of PKCδ in each cellular line.

Abstract

The c-kit inhibitor STI571 represents one of the most important treatments for patients with mastocytosis. However, intracellular pathways modulated by this compound are not completely defined. Here, STI571 effect on Protein Kinase C (PKC) regulation is determined in HMC-1 mast cell lines. STI571 activates PKCδ isoform resulting in HMC-1(560) apoptosis. The apoptosis observed is PKCδ-dependent, since PKCδ-silencing avoids STI571 effect. c-kit inhibition implies nuclear PKCδ translocation characterized by a clear dependence on actin cytoskeleton integrity in HMC-1(560) cell line, but not in HMC-1(560,816). Therefore, PKCδ modulations can lead to a serious decrease in STI571 treatment-effectiveness.

• Authors: Araceli Tobío, Amparo Alfonso, Luis M Botana
• Journal: Cellular immunology (Cell Immunol) Vol. 293 Issue 2 Pg. 104-12 (Feb 2015) ISSN: 1090-2163 [Electronic] Netherlands
• PMID: 25594139 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Benzamides
• Isoenzymes
• Piperazines
• Protein Kinase Inhibitors
• Pyrimidines
• Imatinib Mesylate
• Proto-Oncogene Proteins c-kit
• Protein Kinase C

Topics

• Apoptosis (drug effects, immunology)
• Benzamides (pharmacology)
• Blotting, Western
• Cell Line
• Enzyme Activation (immunology)
• Flow Cytometry
• Humans
• Imatinib Mesylate
• Isoenzymes
• Mast Cells (immunology)
• Piperazines (pharmacology)
• Protein Kinase C (analysis, immunology)
• Protein Kinase Inhibitors (pharmacology)
• Proto-Oncogene Proteins c-kit (immunology)
• Pyrimidines (pharmacology)
• Signal Transduction (immunology)