Localisation of Protein Kinase C in Apoptosis and Neurite Outgrowth

Anna Schultz

Research output: ThesisDoctoral Thesis (compilation)

68 Downloads (Pure)

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. One major aim of this thesis work was to investigate if altered levels of PKC isoforms influence the apoptotic responses of malignant cell-lines. We show that overexpression of PKCd or PKCq renders SK-N-BE(2) neuroblastoma cells sensitive to apoptosis induced by phorbol esters or C2-ceramide. Moreover, overexpression of PKCa, PKCd or PKCe sensitises both androgen-dependent and androgen-independent prostate cancer cells to phorbol ester-induced cell-death. The apoptotic effects of PKCd and PKCq in neuroblastoma cells are independent on the catalytic activity of the enzymes and the isolated regulatory domain (RD) of PKCq induces apoptosis in neuroblastoma cells. Induction of apoptosis depends on the localisation of PKCqRD to the Golgi complex, which is mediated by the C1b domain of the protein. Mutation of a single amino acid residue, Met-267 in PKCqC1b, blocks both the Golgi localisation and the apoptotic effect of the PKCqRD.

Previous studies have shown that PKCe induces neurites in neuroblastoma cells. Here we report that treatment with cell-permeable C2-ceramide inhibits PKCe-induced neurite formation, conceivably by relocating the protein from the cytosol to the perinuclear region. Mutation of Asp-257 and Met-278 (the latter corresponding to Met-267 in PKCq) in PKCe blocks the C2-ceramide induced translocation of PKCe. Furthermore, the mutated variant of PKCe still induces neurites after C2-ceramide treatment. Thus, the specific subcellular localisation of PKCq and PKCe are important for their biological activities.
Original languageEnglish
QualificationDoctor
Awarding Institution
  • Department of Translational Medicine
Supervisors/Advisors
  • Larsson, Christer, Supervisor, External person
Award date2005 May 20
Publisher
Print ISBNs91-85439-36-3
Publication statusPublished - 2005

Bibliographical note

Defence details

Date: 2005-05-20
Time: 09:15
Place: Main Lecture Hall, Pathology Building, University Hospital MAS, Malmö

External reviewer(s)

Name: Iglesias, Teresa
Title: PhD
Affiliation: Universidad Autonóma de Madrid, Spain

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<div class="article_info">Anna Schultz, Jan-Ingvar Jönsson and Christer Larsson. <span class="article_issue_date">2003</span>. <span class="article_title">The regulatory domain of protein kinase C-? localises to the Golgi complex and induces apoptosis in neuroblastoma and Jurkat cells.</span> <span class="journal_series_title">Cell Death. Differ.</span>, <span class="journal_volume">vol 10</span> <span class="journal_pages">pp 662-675</span>.</div>
<div class="article_info">Anna Schultz and Christer Larsson. <span class="article_issue_date">2004</span>. <span class="article_title">Ceramide infl uences neurite outgrowth and neuroblastoma cell apoptosis regulated by novel protein kinase C isoforms.</span> <span class="journal_series_title">J. Neurochem.</span>, <span class="journal_volume">vol 89</span> <span class="journal_pages">pp 1427-1435</span>.</div>
<div class="article_info">Anna Schultz, Mia Ling and Christer Larsson. <span class="article_issue_date">2004</span>. <span class="article_title">Identification of an amino acid residue in the protein kinase C C1b domain crucial for its localization to the Golgi network.</span> <span class="journal_series_title">J. Biol. Chem.</span>, <span class="journal_volume">vol 279</span> <span class="journal_pages">pp 31750-31760</span>.</div>
<div class="article_info">Anna Schultz and Christer Larsson. <span class="article_issue_date"></span>. <span class="article_title">Protein kinase C-? induces cell death both inandrogen-dependent and androgen-independent prostate cancer cells.</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

Keywords

  • onkologi
  • cancer
  • Medicine (human and vertebrates)
  • Medicin (människa och djur)
  • Cytology
  • oncology
  • cancerology
  • Cytologi
  • Prostate Cancer
  • Neuroblastoma
  • Ceramide
  • Golgi Apparatus
  • Neurite outgrowth
  • Apoptosis
  • Protein Kinase C
  • C1 domain

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