ERA

Download the full-sized PDF of Examination of the Regulation of Phosphorylation Events in Macrophage Adhesion and Response to ZymosanDownload the full-sized PDF

Analytics

Share

Permanent link (DOI): https://doi.org/10.7939/R39W6W

Download

Export to: EndNote  |  Zotero  |  Mendeley

Communities

This file is in the following communities:

Graduate Studies and Research, Faculty of

Collections

This file is in the following collections:

Theses and Dissertations

Examination of the Regulation of Phosphorylation Events in Macrophage Adhesion and Response to Zymosan Open Access

Descriptions

Other title
Subject/Keyword
macrophage
CD45
paxillin
Pyk2
adhesion
calpain
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
St-Pierre, Joëlle
Supervisor and department
Ostergaard, Hanne (Medical Microbiology and Immunology)
Examining committee member and department
Pukatzki, Stefan (Medical Microbiology and Immunology)
Magor, Katharine (Biological Sciences)
Burshtyn, Deborah (Medical Microbiology and Immunology)
Johnson, Pauline (Microbiology and Immunology)
Foley, Edan (Medical Microbiology and Immunology)
Department
Department of Medical Microbiology and Immunology
Specialization
Immunology
Date accepted
2012-09-11T15:03:15Z
Graduation date
2012-09
Degree
Doctor of Philosophy
Degree level
Doctoral
Abstract
Macrophages play a central role in innate immunity, most notably in tissue repair, phagocytosis of dead or infected cells, secretion of chemokine and cytokines at sites of infection, as well as the activation of other immune cells. These roles are highly dependent on their capacity to migrate throughout the body by mediating intercellular adhesion and adhesion to the ECM. A comprehensive understanding of the molecular mechanisms of adhesion and motility of macrophages is thus critical to better manipulate the innate immune response. Pyk2 and paxillin are key components of the macrophage cytoskeleton. I demonstrated that Pyk2 is found as two biochemically and spatially distinct populations in macrophages, based on their binding partners, serine/threonine phosphorylation status, and post-translational modifications. I further investigated the role of the protein tyrosine phosphatase CD45 on the regulation of the macrophage cytoskeleton. I found that the absence of CD45 in macrophages leads to defects in adhesion and motility; these defects are possibly due a decrease in paxillin expression. Moreover, inhibition of calpain and Pyk2 activity partially restored paxillin expression in these cells. Finally, I examined whether the absence of CD45 led to defects in macrophage responses to the yeast-derived particle zymosan. No significant differences in cytokine secretion, pathogen recognition receptor expression and rate of phagocytosis were observed in CD45-deficient macrophages. Changes in tyrosine phosphorylation and increased particle binding, however, were observed upon treatment with zymosan. In all, these results underline the contribution of Pyk2 and CD45 in the regulation of macrophage adhesion as well as the role of CD45 in the regulation of macrophage responses to fungal stimulus.
Language
English
DOI
doi:10.7939/R39W6W
Rights
Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
Citation for previous publication
St-Pierre, J., Lysechko, T.L. and H.L. Ostergaard (2011) Hypophosphorylated and inactive Pyk2 associates with paxillin at the microtubule organizing center in hematopoietic cells, Cell Signaling, 23(4):718-30

File Details

Date Uploaded
Date Modified
2014-04-24T23:12:08.415+00:00
Audit Status
Audits have not yet been run on this file.
Characterization
File format: pdf (Portable Document Format)
Mime type: application/pdf
File size: 24373747
Last modified: 2015:10:12 12:10:43-06:00
Filename: St-Pierre_Joelle_Fall 2012.pdf
Original checksum: 0c03449198c5148e549d57d3b253fc85
Well formed: true
Valid: true
Status message: File header gives version as 1.5, but catalog dictionary gives version as 1.3
Status message: Too many fonts to report; some fonts omitted. Total fonts = 1072
File title: JSP THESIS FINAL
File author: Joelle St-Pierre
Page count: 213
Activity of users you follow
User Activity Date