Abstract
Protein kinase C (PKC) is a family of serine/threonine kinases involved in the transduction of a variety of signals. There is increasing evidence to indicate that specific PKC isoforms are involved in the regulation of distinct cellular processes. In glioma cells, PKC α was found to be a critical regulator of proliferation and cell cycle progression, while PKC ε was found to regulate adhesion and migration. Herein, we report that specific PKC isoforms are able to differentially activate extracellular-signal regulated kinase (ERK) in distinct cellular locations: while PKC α induces the activation of nuclear ERK, PKC ε induces the activation of ERK at focal adhesions. Inhibition of the ERK pathway completely abolished the PKC-induced integrin-mediated adhesion and migration. Thus, we present the first evidence that PKC ε is able to activate ERK at focal adhesions to mediate glioma cell adhesion and motility, providing a molecular mechanism to explain the different biological functions of PKC α and ε in glioma cells.
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Acknowledgements
We gratefully thank Tammy L Wilson for technical assistance in the adhesion assays. This work is supported by a grant from the Canadian Institutes for Health Research. A Besson is a Research Student of the National Cancer Institute of Canada supported with funds provided by the Terry Fox Run. A Davy is the recipient of an Alberta Cancer Board postdoctoral fellowship. SM Robbins is a scholar of the Alberta Heritage Foundation for Medical Research and holds a Canada Research Chair in Cancer Biology. VW Yong is a Medical Research Council of Canada Scientist and a senior scholar of the Alberta Heritage Foundation for Medical Research.
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Besson, A., Davy, A., Robbins, S. et al. Differential activation of ERKs to focal adhesions by PKC ε is required for PMA-induced adhesion and migration of human glioma cells. Oncogene 20, 7398–7407 (2001). https://doi.org/10.1038/sj.onc.1204899
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DOI: https://doi.org/10.1038/sj.onc.1204899
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