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Protein Kinase Cepsilon Actin-binding Site Is Important for Neurite Outgrowth during Neuronal Differentiation.

Zeidman, Ruth LU ; Trollér, Ulrika LU ; Raghunath, Arathi; Påhlman, Sven LU and Larsson, Christer LU (2002) In Molecular Biology of the Cell 13(1). p.12-24
Abstract
We have previously shown that protein kinase Cepsilon (PKCepsilon) induces neurite outgrowth via its regulatory domain and independently of its kinase activity. This study aimed at identifying mechanisms regulating PKCepsilon-mediated neurite induction. We show an increased association of PKCepsilon to the cytoskeleton during neuronal differentiation. Furthermore, neurite induction by overexpression of full-length PKCepsilon is suppressed if serum is removed from the cultures or if an actin-binding site is deleted from the protein. A peptide corresponding to the PKCepsilon actin-binding site suppresses neurite outgrowth during neuronal differentiation and outgrowth elicited by PKCepsilon overexpression. Neither serum removal, deletion of... (More)
We have previously shown that protein kinase Cepsilon (PKCepsilon) induces neurite outgrowth via its regulatory domain and independently of its kinase activity. This study aimed at identifying mechanisms regulating PKCepsilon-mediated neurite induction. We show an increased association of PKCepsilon to the cytoskeleton during neuronal differentiation. Furthermore, neurite induction by overexpression of full-length PKCepsilon is suppressed if serum is removed from the cultures or if an actin-binding site is deleted from the protein. A peptide corresponding to the PKCepsilon actin-binding site suppresses neurite outgrowth during neuronal differentiation and outgrowth elicited by PKCepsilon overexpression. Neither serum removal, deletion of the actin-binding site, nor introduction of the peptide affects neurite induction by the isolated regulatory domain. Membrane targeting by myristoylation renders full-length PKCepsilon independent of both serum and the actin-binding site, and PKCepsilon colocalized with F-actin at the cortical cytoskeleton during neurite outgrowth. These results demonstrate that the actin-binding site is of importance for signals acting on PKCepsilon in a pathway leading to neurite outgrowth. Localization of PKCepsilon to the plasma membrane and/or the cortical cytoskeleton is conceivably important for its effect on neurite outgrowth. (Less)
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organization
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published
subject
keywords
Image Cytometry, Microscopy, Confocal, Fluorescence, Neurites/*physiology, Neuroblastoma, Protein Conformation, Protein Kinase C/*chemistry/genetics/*metabolism, Recombinant Fusion Proteins/metabolism, Substrate Specificity, Support, Non-U.S. Gov't, Transfection, Cultured, Tumor Cells, Isoenzymes/*chemistry/genetics/*metabolism, Human, Cytoskeleton/metabolism, Cell Differentiation/physiology, Binding Sites, Actins/*metabolism
in
Molecular Biology of the Cell
volume
13
issue
1
pages
12 - 24
publisher
American Society for Cell Biology
external identifiers
  • wos:000173402000002
  • pmid:11809819
  • scopus:0036007287
ISSN
1939-4586
DOI
10.1091/mbc.01-04-0210
language
English
LU publication?
yes
id
e7050503-30b8-4232-9fad-6c1e1fc481dd (old id 106461)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11809819&dopt=Abstract
date added to LUP
2007-07-27 14:07:00
date last changed
2017-02-26 03:24:11
@article{e7050503-30b8-4232-9fad-6c1e1fc481dd,
  abstract     = {We have previously shown that protein kinase Cepsilon (PKCepsilon) induces neurite outgrowth via its regulatory domain and independently of its kinase activity. This study aimed at identifying mechanisms regulating PKCepsilon-mediated neurite induction. We show an increased association of PKCepsilon to the cytoskeleton during neuronal differentiation. Furthermore, neurite induction by overexpression of full-length PKCepsilon is suppressed if serum is removed from the cultures or if an actin-binding site is deleted from the protein. A peptide corresponding to the PKCepsilon actin-binding site suppresses neurite outgrowth during neuronal differentiation and outgrowth elicited by PKCepsilon overexpression. Neither serum removal, deletion of the actin-binding site, nor introduction of the peptide affects neurite induction by the isolated regulatory domain. Membrane targeting by myristoylation renders full-length PKCepsilon independent of both serum and the actin-binding site, and PKCepsilon colocalized with F-actin at the cortical cytoskeleton during neurite outgrowth. These results demonstrate that the actin-binding site is of importance for signals acting on PKCepsilon in a pathway leading to neurite outgrowth. Localization of PKCepsilon to the plasma membrane and/or the cortical cytoskeleton is conceivably important for its effect on neurite outgrowth.},
  author       = {Zeidman, Ruth and Trollér, Ulrika and Raghunath, Arathi and Påhlman, Sven and Larsson, Christer},
  issn         = {1939-4586},
  keyword      = {Image Cytometry,Microscopy,Confocal,Fluorescence,Neurites/*physiology,Neuroblastoma,Protein Conformation,Protein Kinase C/*chemistry/genetics/*metabolism,Recombinant Fusion Proteins/metabolism,Substrate Specificity,Support,Non-U.S. Gov't,Transfection,Cultured,Tumor Cells,Isoenzymes/*chemistry/genetics/*metabolism,Human,Cytoskeleton/metabolism,Cell Differentiation/physiology,Binding Sites,Actins/*metabolism},
  language     = {eng},
  number       = {1},
  pages        = {12--24},
  publisher    = {American Society for Cell Biology},
  series       = {Molecular Biology of the Cell},
  title        = {Protein Kinase Cepsilon Actin-binding Site Is Important for Neurite Outgrowth during Neuronal Differentiation.},
  url          = {http://dx.doi.org/10.1091/mbc.01-04-0210},
  volume       = {13},
  year         = {2002},
}