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Cell Growth & Differentiation Vol. 10, 183-191, March 1999
© 1999 American Association for Cancer Research

Protein Kinase C-{epsilon} Plays a Role in Neurite Outgrowth in Response to Epidermal Growth Factor and Nerve Growth Factor in PC12 Cells

Chaya Brodie, Krisztina Bogi, Peter Acs, Philip Lazarovici, Gyorgy Petrovics, Wayne B. Anderson and Peter M. Blumberg1

Molecular Mechanisms of Tumor Promotion Section, LCCTP [C. B., K. B., P. A., P. M. B.] and Signal Transduction Section, LCO [G. P., W. B. A.], National Cancer Institute, NIH, Bethesda, Maryland 20892, and Gonda-Goldschmied Center, Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel [C. B., P. L.]

In this study, we examined the role of specific protein kinase C (PKC) isoforms in the differentiation of PC12 cells in response to nerve growth factor (NGF) and epidermal growth factor (EGF). PC12 cells express PKC-{alpha}, -ß, -{gamma}, -{delta}, -{epsilon}, -µ, and -{zeta}. For PKC-{delta}, -{epsilon}, and -{zeta}, NGF and EGF exerted differential effects on translocation. Unlike overexpression of PKC-{alpha} and -{delta}, overexpression of PKC-{epsilon} caused enhanced neurite outgrowth in response to NGF. In the PKC-{epsilon}-overexpressing cells, EGF also dramatically induced neurite outgrowth, arrested cell proliferation, and induced a sustained phosphorylation of mitogen-activated protein kinase (MAPK), in contrast to its mitogenic effects on control cells or cells overexpressing PKC-{alpha} and -{delta}. The induction of neurite outgrowth by EGF was inhibited by the MAPK kinase inhibitor PD95098. In cells overexpressing a PKC-{epsilon} dominant negative mutant, NGF induced reduced neurite outgrowth and a more transient phosphorylation of MAPK than in controls. Our results suggest an important role for PKC-{epsilon} in neurite outgrowth in PC12 cells, probably via activation of the MAPK pathway.




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Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 1999 by the American Association of Cancer Research.