Advanced

The molecular features in PKC epsilon determining its neurite-inducing capacity

Ling, Mia LU (2005)
Abstract
Protein kinase C (PKC) is a family of serine/threonine kinases which are subgrouped into classical (a, bI, bII, g), novel (d, e, h, q) and atypical (z, i/l) isoforms.



It has been shown that PKCe induces neurite outgrowth in neuroblastoma cells and the effect is mediated via the regulatory domain. One aim of this study was to identify the structures in PKCe that mediate neurite outgrowth. This study shows that PKCe-induced neurite outgrowth can be obtained in several other neural cell lines and that PKC catalytic activity and the RhoA pathway can counteract neurite outgrowth. A region of PKCe encompassing the two C1 domains and flanking residues was shown to be sufficient for neurite induction. The corresponding region... (More)
Protein kinase C (PKC) is a family of serine/threonine kinases which are subgrouped into classical (a, bI, bII, g), novel (d, e, h, q) and atypical (z, i/l) isoforms.



It has been shown that PKCe induces neurite outgrowth in neuroblastoma cells and the effect is mediated via the regulatory domain. One aim of this study was to identify the structures in PKCe that mediate neurite outgrowth. This study shows that PKCe-induced neurite outgrowth can be obtained in several other neural cell lines and that PKC catalytic activity and the RhoA pathway can counteract neurite outgrowth. A region of PKCe encompassing the two C1 domains and flanking residues was shown to be sufficient for neurite induction. The corresponding region from all novel PKC isoforms, but not PKCa, had neurite-inducing capacity. Furthermore, a conserved motif immediately N-terminal of the PKCe C1b domain, was found to be required for neurite induction, and specifically, mutation of either Phe-237, Val-239 or Met-241 within this motif abolished neurite outgrowth. The isolated PKCe C1b domain including twelve N-terminal and twenty C-terminal residues could induce neurite outgrowth in the presence of phorbol ester. It was also shown that specific structures in the PKCe C1b domain are required for neurite induction. Residues in the C-terminal end of the PKCe C1b domain localised at the base of the globular C1 domain, in the proximity of the motif N-terminal of the C1b domain, were identified as important for neurite outgrowth. Thus individual residues determining isoform-specific effects of PKC have been identified. (Less)
Please use this url to cite or link to this publication:
author
opponent
  • Dr Hall, Christine, Inst of Neurology, University College London, UK
organization
publishing date
type
Thesis
publication status
published
subject
keywords
oncology, Cytology, neuroblastoma, neurite outgrowth, C1 domain, cancerology, cancer, onkologi, Cytologi, protein kinase C
pages
95 pages
publisher
Division of Molecular Medicine, Department of Laboratory Medicine, UMAS, Malmö
defense location
Föreläsningssalen, Patologihuset, Universitetssjukhuset MAS, Malmö.
defense date
2005-12-16 09:15
ISSN
1652-8220
ISBN
91-85481-22-x
language
English
LU publication?
yes
id
e2fd2695-712d-4101-b264-f403edd970c9 (old id 545911)
date added to LUP
2007-09-20 15:54:14
date last changed
2016-09-19 08:44:55
@phdthesis{e2fd2695-712d-4101-b264-f403edd970c9,
  abstract     = {Protein kinase C (PKC) is a family of serine/threonine kinases which are subgrouped into classical (a, bI, bII, g), novel (d, e, h, q) and atypical (z, i/l) isoforms.<br/><br>
<br/><br>
It has been shown that PKCe induces neurite outgrowth in neuroblastoma cells and the effect is mediated via the regulatory domain. One aim of this study was to identify the structures in PKCe that mediate neurite outgrowth. This study shows that PKCe-induced neurite outgrowth can be obtained in several other neural cell lines and that PKC catalytic activity and the RhoA pathway can counteract neurite outgrowth. A region of PKCe encompassing the two C1 domains and flanking residues was shown to be sufficient for neurite induction. The corresponding region from all novel PKC isoforms, but not PKCa, had neurite-inducing capacity. Furthermore, a conserved motif immediately N-terminal of the PKCe C1b domain, was found to be required for neurite induction, and specifically, mutation of either Phe-237, Val-239 or Met-241 within this motif abolished neurite outgrowth. The isolated PKCe C1b domain including twelve N-terminal and twenty C-terminal residues could induce neurite outgrowth in the presence of phorbol ester. It was also shown that specific structures in the PKCe C1b domain are required for neurite induction. Residues in the C-terminal end of the PKCe C1b domain localised at the base of the globular C1 domain, in the proximity of the motif N-terminal of the C1b domain, were identified as important for neurite outgrowth. Thus individual residues determining isoform-specific effects of PKC have been identified.},
  author       = {Ling, Mia},
  isbn         = {91-85481-22-x},
  issn         = {1652-8220},
  keyword      = {oncology,Cytology,neuroblastoma,neurite outgrowth,C1 domain,cancerology,cancer,onkologi,Cytologi,protein kinase C},
  language     = {eng},
  pages        = {95},
  publisher    = {Division of Molecular Medicine, Department of Laboratory Medicine, UMAS, Malmö},
  school       = {Lund University},
  title        = {The molecular features in PKC epsilon determining its neurite-inducing capacity},
  year         = {2005},
}