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Distinct roles of PKC isoforms in NCAM-mediated neurite outgrowth

Kolkova, K; Stensman, Helena LU ; Berezin, V; Bock, E and Larsson, Christer LU (2005) In Journal of Neurochemistry 92(4). p.886-894
Abstract
The role of protein kinase C (PKC) isoforms in the neural cell adhesion molecule (NCAM)-mediated neurite outgrowth was tested using a co-culture system consisting of fibroblasts with or without NCAM expression upon which either primary cerebellar granular neurones (CGN) or pheochromocytoma (PC12-E2) cells were grown. The latter transiently expressed various PKC isoforms and domains derived from selected PKCs. PKC inhibitors of various specificity inhibited NCAM-stimulated neuritogenesis from CGN, indicating that PKC is involved in this process. Moreover, stimulation by the NCAM-mimetic peptide, C3d, elicited phosphorylation of PKC in CGN. Expression of kinase-deficient forms of PKCalpha, betaI and betaII blocked NCAM-mediated neurite... (More)
The role of protein kinase C (PKC) isoforms in the neural cell adhesion molecule (NCAM)-mediated neurite outgrowth was tested using a co-culture system consisting of fibroblasts with or without NCAM expression upon which either primary cerebellar granular neurones (CGN) or pheochromocytoma (PC12-E2) cells were grown. The latter transiently expressed various PKC isoforms and domains derived from selected PKCs. PKC inhibitors of various specificity inhibited NCAM-stimulated neuritogenesis from CGN, indicating that PKC is involved in this process. Moreover, stimulation by the NCAM-mimetic peptide, C3d, elicited phosphorylation of PKC in CGN. Expression of kinase-deficient forms of PKCalpha, betaI and betaII blocked NCAM-mediated neurite extension, but had no effect on nerve growth factor (NGF)-mediated neurite outgrowth. Expression of two PKCepsilon constructs: (i) a fragment from PKCepsilon encompassing the pseudosubstrate, the C1a domain (including the actin-binding site, ABS), and parts of the V3 region, or (ii) the PKCepsilon-specific ABS blocked NCAM-mediated neurite extension in both cases. These two constructs also partially inhibited NGF-stimulated neuritogenesis indicating that PKCepsilon is a positive regulator of both NCAM- and NGF-mediated differentiation. We suggest that PKCepsilon is a common downstream mediator for several neuritogenic factors, whereas one or more conventional PKCs are specifically involved in NCAM-stimulated neurite outgrowth. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
pheochromocytoma cells, outgrowth, neural cell adhesion molecule, neurite, cerebellar granular neurones, protein kinase C
in
Journal of Neurochemistry
volume
92
issue
4
pages
886 - 894
publisher
Wiley-Blackwell
external identifiers
  • pmid:15686491
  • wos:000226706600020
  • scopus:13644266768
ISSN
1471-4159
DOI
10.1111/j.1471-4159.2004.02919.x
language
English
LU publication?
yes
id
cfb3d0d0-74a5-4e5f-9caa-974ce3c20ce3 (old id 254312)
date added to LUP
2007-08-09 15:36:38
date last changed
2017-07-30 04:35:48
@article{cfb3d0d0-74a5-4e5f-9caa-974ce3c20ce3,
  abstract     = {The role of protein kinase C (PKC) isoforms in the neural cell adhesion molecule (NCAM)-mediated neurite outgrowth was tested using a co-culture system consisting of fibroblasts with or without NCAM expression upon which either primary cerebellar granular neurones (CGN) or pheochromocytoma (PC12-E2) cells were grown. The latter transiently expressed various PKC isoforms and domains derived from selected PKCs. PKC inhibitors of various specificity inhibited NCAM-stimulated neuritogenesis from CGN, indicating that PKC is involved in this process. Moreover, stimulation by the NCAM-mimetic peptide, C3d, elicited phosphorylation of PKC in CGN. Expression of kinase-deficient forms of PKCalpha, betaI and betaII blocked NCAM-mediated neurite extension, but had no effect on nerve growth factor (NGF)-mediated neurite outgrowth. Expression of two PKCepsilon constructs: (i) a fragment from PKCepsilon encompassing the pseudosubstrate, the C1a domain (including the actin-binding site, ABS), and parts of the V3 region, or (ii) the PKCepsilon-specific ABS blocked NCAM-mediated neurite extension in both cases. These two constructs also partially inhibited NGF-stimulated neuritogenesis indicating that PKCepsilon is a positive regulator of both NCAM- and NGF-mediated differentiation. We suggest that PKCepsilon is a common downstream mediator for several neuritogenic factors, whereas one or more conventional PKCs are specifically involved in NCAM-stimulated neurite outgrowth.},
  author       = {Kolkova, K and Stensman, Helena and Berezin, V and Bock, E and Larsson, Christer},
  issn         = {1471-4159},
  keyword      = {pheochromocytoma cells,outgrowth,neural cell adhesion molecule,neurite,cerebellar granular neurones,protein kinase C},
  language     = {eng},
  number       = {4},
  pages        = {886--894},
  publisher    = {Wiley-Blackwell},
  series       = {Journal of Neurochemistry},
  title        = {Distinct roles of PKC isoforms in NCAM-mediated neurite outgrowth},
  url          = {http://dx.doi.org/10.1111/j.1471-4159.2004.02919.x},
  volume       = {92},
  year         = {2005},
}