These studies examined the extent to which protein kinase C (PKC) and cAMP-dependent protein kinase (PKA) regulate the neuronal differentiation of the raphe-derived neuronal cell line, RN33B. A differentiation-specific 2.25-fold increase in soluble PKA activity was observed. Neither membrane-associa
Regulation of neuronal differentiation by the α and ϵ isoforms of protein kinase C
✍ Scribed by John J. Boyce; David J. Ennulat; Ubaldo Leli; Thomas B. Shea
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- English
- Weight
- 594 KB
- Volume
- 18
- Category
- Article
- ISSN
- 0893-6609
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✦ Synopsis
Previous studies utilizing cell-permeant inhibitors and intracellular delivery of anti-PKC antibodies and active enzyme have indicated that inhibition of protein kinase C (PKC) promotes the initial stage(s) of neurite elaboration, while PKC activation inhibits and reverses this phenomenon. In the present study we treated SH-SY-SY human neuroblastoma cells with antisense oligonucleotides directed against unique sequences of the a, 0, and E PKC isoforms for a length of time (5 days) sufficient to reduce imunocytochemical levels of their specific target isoforms. We observed that treatment for 5 days with antisense oligonucleotides directed against PKCa and PKCE, but not PKCp, induced a marked increase in the percentage of cells elaborating neurites. By contrast, treatment with the corresponding sense-oriented oligonucleotides for each isoform had no detectable effect. These data confirm the participation of PKC in regulation of the initial stage(s) of neuronal differentiation, and further imply specific roles for the PKCa and E isoforms in this regulation.
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