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 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.
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.
| Original language | English |
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| Qualification | Doctor |
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| Award date | 2005 Dec 16 |
| Publisher | |
| ISBN (Print) | 91-85481-22-x |
| Publication status | Published - 2005 |
Bibliographical note
Defence detailsDate: 2005-12-16
Time: 09:15
Place: Föreläsningssalen, Patologihuset, Universitetssjukhuset MAS, Malmö.
External reviewer(s)
Name: Hall, Christine
Title: Dr
Affiliation: Inst of Neurology, University College London, UK
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<div class="article_info">Mia Ling. <span class="article_issue_date">2004</span>. <span class="article_title">Induction of neurites by the regulatory domains of PKC? and ? is counteracted by PKC catalytic activity and by the RhoA pathway.</span> <span class="journal_series_title">Exp Cell Res.</span>, <span class="journal_volume">vol 292</span> <span class="journal_pages">pp 135-150</span>.</div>
<div class="article_info">Mia Ling, Ulrika Trollér, Ruth Zeidman, Cecilia Lundberg and Christer Larsson. <span class="article_issue_date">2004</span>. <span class="article_title">Induction of neurites by the regulatory domains of PKC? and ? is counteracted by PKC catalytic activity and by the RhoA pathway.</span> <span class="journal_series_title">Exp Cell Res.</span>, <span class="journal_volume">vol 292</span> <span class="journal_pages">pp 135-150</span>.</div>
<div class="article_info">Mia Ling, Ulrika Trollér, Ruth Zeidman, Helena Stensman, Anna Schultz and Christer Larsson. <span class="article_issue_date">2005</span>. <span class="article_title">Identifi cation of conserved amino acids N-terminal of the PKC? C1b domain crucial for PKC?-mediated neurite outgrowth.</span> <span class="journal_series_title">J Biol Chem</span>, <span class="journal_volume">vol 280</span> <span class="journal_pages">pp 17910-17919</span>.</div>
<div class="article_info">Mia Ling and Christer Larsson. <span class="article_issue_date"></span>. <span class="article_title">Comparison of the PKC? and PKC? C1b domains: Identifi cation of residues critical for PKC?-mediated neurite induction.</span> (manuscript)</div>
The information about affiliations in this record was updated in December 2015.
The record was previously connected to the following departments: Molecular Medicine (013031200)
Subject classification (UKÄ)
- Cancer and Oncology
Free keywords
- oncology
- Cytology
- neuroblastoma
- neurite outgrowth
- C1 domain
- cancerology
- cancer
- onkologi
- Cytologi
- protein kinase C
