{"id":{"repo_id":"dundee","oai_identifier":"oai:discovery.dundee.ac.uk:studenttheses/8fc76d1f-a0a4-4756-a6ca-fe9fcf659751"},"canonical_url":"https://search.dev.ndltd.org/etd/dundee/oai:discovery.dundee.ac.uk:studenttheses/8fc76d1f-a0a4-4756-a6ca-fe9fcf659751","repository":{"repo_id":"dundee","name":"University of Dundee","base_url":"https://discovery.dundee.ac.uk/ws/oai"},"display":{"title":"The role of extracellular signal-regulated kinases (ERKs) in T lymphocytes","abstract":"The aim of this study was to evaluate the role of the MAP kinases ERK1/2 in naïve and effector CD8 T lymphocytes. Initial experiments showed that inhibition of ERK1/2 activation impaired protein synthesis and reduced cell growth and proliferation of T cell antigen receptor (TCR) stimulated naïve CD8 T cells. On the basis of this data, proteomics analysis of the impact of inhibiting ERK1/2 on the TCR stimulated CD8 T cell proteome was performed. These studies identified 8609 proteins in TCR activated CD8 T cells. The impact of ERK1/2 inhibition was to reduce expression of 1910 proteins and increase expression of 220 proteins. The proteins whose expression was reduced in TCR activated T cells lacking active ERK1/2 proteins included eukaryotic initiation factors, glucose and amino acid transporters, cytokines like IL-2, cytolytic molecules such as granzyme B, surface molecules such as CD25 and transcription factors like EGR1. These results provide a comprehensive understanding of the role of ERK1/2 in antigen receptor signaling in naïve T cells.<br/><br/>The second part of this study consisted of the evaluation of the ERK1/2 role in TCR activated cytotoxic T lymphocytes (CTLs). These studies identified 7627 proteins in TCR re triggered CTLs. The impact of ERK1/2 inhibition was to reduce expression of 101 proteins and increase expression of 75 proteins.The proteins whose expression was reduced in TCR re-triggered CTLs lacking active ERK1/2 proteins included cytokines, chemokines, and transcription factors. However, loss of ERK1/2 activity did not affect expression of eukaryotic initiation proteins, cytolytic molecules and amino acid or glucose transporters. These data provide a comprehensive understanding of the role of ERK1/2 in antigen receptor signaling in CTL and reveal differences in the impact of ERK1/2 inhibition in naive T cells versus effector CTL.<br/><br/>ERK1/2 phosphorylates different substrates, including the p90 ribosomal S6 kinases (RSKs).In the last part of this study I used genetically modified mice to evaluate whether the effects caused by inhibition of MEK1/2 in T cells are mediated by RSKs. T cells express RSK1 and RSK2. The data show no discernible impact of deleting RSK1 on T cell phenotypes. TCR activated RSK2 in null T cells showed reduced production of IL-2, which suggests that RSK2 mediates production of this cytokine downstream of ERK1/2. However, deletion of RSKs did not phenocopy the effects of ERK1/2 inhibition on TCR induced cell growth and proliferation. Hence, further studies are required to identify relevant ERK1/2 substrates in T cells.","abstract_html":"The aim of this study was to evaluate the role of the MAP kinases ERK1/2 in naïve and effector CD8 T lymphocytes. Initial experiments showed that inhibition of ERK1/2 activation impaired protein synthesis and reduced cell growth and proliferation of T cell antigen receptor (TCR) stimulated naïve CD8 T cells. On the basis of this data, proteomics analysis of the impact of inhibiting ERK1/2 on the TCR stimulated CD8 T cell proteome was performed. These studies identified 8609 proteins in TCR activated CD8 T cells. The impact of ERK1/2 inhibition was to reduce expression of 1910 proteins and increase expression of 220 proteins. The proteins whose expression was reduced in TCR activated T cells lacking active ERK1/2 proteins included eukaryotic initiation factors, glucose and amino acid transporters, cytokines like IL-2, cytolytic molecules such as granzyme B, surface molecules such as CD25 and transcription factors like EGR1. These results provide a comprehensive understanding of the role of ERK1/2 in antigen receptor signaling in naïve T cells.&lt;br/&gt;&lt;br/&gt;The second part of this study consisted of the evaluation of the ERK1/2 role in TCR activated cytotoxic T lymphocytes (CTLs). These studies identified 7627 proteins in TCR re triggered CTLs. The impact of ERK1/2 inhibition was to reduce expression of 101 proteins and increase expression of 75 proteins.The proteins whose expression was reduced in TCR re-triggered CTLs lacking active ERK1/2 proteins included cytokines, chemokines, and transcription factors. However, loss of ERK1/2 activity did not affect expression of eukaryotic initiation proteins, cytolytic molecules and amino acid or glucose transporters. These data provide a comprehensive understanding of the role of ERK1/2 in antigen receptor signaling in CTL and reveal differences in the impact of ERK1/2 inhibition in naive T cells versus effector CTL.&lt;br/&gt;&lt;br/&gt;ERK1/2 phosphorylates different substrates, including the p90 ribosomal S6 kinases (RSKs).In the last part of this study I used genetically modified mice to evaluate whether the effects caused by inhibition of MEK1/2 in T cells are mediated by RSKs. T cells express RSK1 and RSK2. The data show no discernible impact of deleting RSK1 on T cell phenotypes. TCR activated RSK2 in null T cells showed reduced production of IL-2, which suggests that RSK2 mediates production of this cytokine downstream of ERK1/2. However, deletion of RSKs did not phenocopy the effects of ERK1/2 inhibition on TCR induced cell growth and proliferation. Hence, further studies are required to identify relevant ERK1/2 substrates in T cells.","abstract_has_math":false,"creators":["de Souza Damasio, Marcos Paulo"],"institution":"University of Dundee","degree_name":"Doctor of Philosophy","degree_level":"Doctoral Thesis","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Cantrell, Doreen"],"committee_chairs":[],"committee_members":[],"year":2016,"date_issued":"2016","date_published":"2016","updated_at":"2026-07-24T02:08:26Z","subjects":[],"languages":["eng"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["oai:discovery.dundee.ac.uk:studenttheses/8fc76d1f-a0a4-4756-a6ca-fe9fcf659751"],"render_values":[{"text":"oai:discovery.dundee.ac.uk:studenttheses/8fc76d1f-a0a4-4756-a6ca-fe9fcf659751","href":null,"code":true}]}]},"links":{"outbound_url":"https://discovery.dundee.ac.uk/en/studentTheses/8fc76d1f-a0a4-4756-a6ca-fe9fcf659751","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Cantrell, Doreen"]},{"key":"dc:creator","label":"Author","values":["de Souza Damasio, Marcos Paulo"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2016"]},{"key":"dc:date.issued","label":"Date","values":["2016"]},{"key":"dc:publisher.department","label":"Dc Publisher Department","values":["Cell Signalling and Immunology"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["University of Dundee"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["https://discovery.dundee.ac.uk/en/studentTheses/8fc76d1f-a0a4-4756-a6ca-fe9fcf659751"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["Doctoral Thesis"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["Doctor of Philosophy"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights.embargodate","label":"Dc Rights Embargodate","values":["2019-06-30"]},{"key":"dc:rights.embargoreason","label":"Dc Rights Embargoreason","values":["/dk/atira/pure/core/document/studentthesisembargoreason/commercialexploitation"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["oai:discovery.dundee.ac.uk:studenttheses/8fc76d1f-a0a4-4756-a6ca-fe9fcf659751","https://discovery.dundee.ac.uk/en/studentTheses/8fc76d1f-a0a4-4756-a6ca-fe9fcf659751"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://discovery.dundee.ac.uk/files/12542045/PhD_Thesis_Marcos_Damasio.pdf"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The aim of this study was to evaluate the role of the MAP kinases ERK1/2 in naïve and effector CD8 T lymphocytes. Initial experiments showed that inhibition of ERK1/2 activation impaired protein synthesis and reduced cell growth and proliferation of T cell antigen receptor (TCR) stimulated naïve CD8 T cells. On the basis of this data, proteomics analysis of the impact of inhibiting ERK1/2 on the TCR stimulated CD8 T cell proteome was performed. These studies identified 8609 proteins in TCR activated CD8 T cells. The impact of ERK1/2 inhibition was to reduce expression of 1910 proteins and increase expression of 220 proteins. The proteins whose expression was reduced in TCR activated T cells lacking active ERK1/2 proteins included eukaryotic initiation factors, glucose and amino acid transporters, cytokines like IL-2, cytolytic molecules such as granzyme B, surface molecules such as CD25 and transcription factors like EGR1. These results provide a comprehensive understanding of the role of ERK1/2 in antigen receptor signaling in naïve T cells.<br/><br/>The second part of this study consisted of the evaluation of the ERK1/2 role in TCR activated cytotoxic T lymphocytes (CTLs). These studies identified 7627 proteins in TCR re triggered CTLs. The impact of ERK1/2 inhibition was to reduce expression of 101 proteins and increase expression of 75 proteins.The proteins whose expression was reduced in TCR re-triggered CTLs lacking active ERK1/2 proteins included cytokines, chemokines, and transcription factors. However, loss of ERK1/2 activity did not affect expression of eukaryotic initiation proteins, cytolytic molecules and amino acid or glucose transporters. These data provide a comprehensive understanding of the role of ERK1/2 in antigen receptor signaling in CTL and reveal differences in the impact of ERK1/2 inhibition in naive T cells versus effector CTL.<br/><br/>ERK1/2 phosphorylates different substrates, including the p90 ribosomal S6 kinases (RSKs).In the last part of this study I used genetically modified mice to evaluate whether the effects caused by inhibition of MEK1/2 in T cells are mediated by RSKs. T cells express RSK1 and RSK2. The data show no discernible impact of deleting RSK1 on T cell phenotypes. TCR activated RSK2 in null T cells showed reduced production of IL-2, which suggests that RSK2 mediates production of this cytokine downstream of ERK1/2. However, deletion of RSKs did not phenocopy the effects of ERK1/2 inhibition on TCR induced cell growth and proliferation. Hence, further studies are required to identify relevant ERK1/2 substrates in T cells."]},{"key":"dc:title","label":"Title","values":["The role of extracellular signal-regulated kinases (ERKs) in T lymphocytes"]}]}],"canonical_facts":{"dc:contributor.advisor":["Cantrell, Doreen"],"dc:creator":["de Souza Damasio, Marcos Paulo"],"dc:date":["2016"],"dc:date.issued":["2016"],"dc:description.abstract":["The aim of this study was to evaluate the role of the MAP kinases ERK1/2 in naïve and effector CD8 T lymphocytes. Initial experiments showed that inhibition of ERK1/2 activation impaired protein synthesis and reduced cell growth and proliferation of T cell antigen receptor (TCR) stimulated naïve CD8 T cells. On the basis of this data, proteomics analysis of the impact of inhibiting ERK1/2 on the TCR stimulated CD8 T cell proteome was performed. These studies identified 8609 proteins in TCR activated CD8 T cells. The impact of ERK1/2 inhibition was to reduce expression of 1910 proteins and increase expression of 220 proteins. The proteins whose expression was reduced in TCR activated T cells lacking active ERK1/2 proteins included eukaryotic initiation factors, glucose and amino acid transporters, cytokines like IL-2, cytolytic molecules such as granzyme B, surface molecules such as CD25 and transcription factors like EGR1. These results provide a comprehensive understanding of the role of ERK1/2 in antigen receptor signaling in naïve T cells.<br/><br/>The second part of this study consisted of the evaluation of the ERK1/2 role in TCR activated cytotoxic T lymphocytes (CTLs). These studies identified 7627 proteins in TCR re triggered CTLs. The impact of ERK1/2 inhibition was to reduce expression of 101 proteins and increase expression of 75 proteins.The proteins whose expression was reduced in TCR re-triggered CTLs lacking active ERK1/2 proteins included cytokines, chemokines, and transcription factors. However, loss of ERK1/2 activity did not affect expression of eukaryotic initiation proteins, cytolytic molecules and amino acid or glucose transporters. These data provide a comprehensive understanding of the role of ERK1/2 in antigen receptor signaling in CTL and reveal differences in the impact of ERK1/2 inhibition in naive T cells versus effector CTL.<br/><br/>ERK1/2 phosphorylates different substrates, including the p90 ribosomal S6 kinases (RSKs).In the last part of this study I used genetically modified mice to evaluate whether the effects caused by inhibition of MEK1/2 in T cells are mediated by RSKs. T cells express RSK1 and RSK2. The data show no discernible impact of deleting RSK1 on T cell phenotypes. TCR activated RSK2 in null T cells showed reduced production of IL-2, which suggests that RSK2 mediates production of this cytokine downstream of ERK1/2. However, deletion of RSKs did not phenocopy the effects of ERK1/2 inhibition on TCR induced cell growth and proliferation. Hence, further studies are required to identify relevant ERK1/2 substrates in T cells."],"dc:identifier":["oai:discovery.dundee.ac.uk:studenttheses/8fc76d1f-a0a4-4756-a6ca-fe9fcf659751","https://discovery.dundee.ac.uk/en/studentTheses/8fc76d1f-a0a4-4756-a6ca-fe9fcf659751"],"dc:identifier.uri":["https://discovery.dundee.ac.uk/files/12542045/PhD_Thesis_Marcos_Damasio.pdf"],"dc:language":["eng"],"dc:publisher.department":["Cell Signalling and Immunology"],"dc:publisher.institution":["University of Dundee"],"dc:relation.isreferencedby":["https://discovery.dundee.ac.uk/en/studentTheses/8fc76d1f-a0a4-4756-a6ca-fe9fcf659751"],"dc:rights.embargodate":["2019-06-30"],"dc:rights.embargoreason":["/dk/atira/pure/core/document/studentthesisembargoreason/commercialexploitation"],"dc:title":["The role of extracellular signal-regulated kinases (ERKs) in T lymphocytes"],"dc:type":["Thesis"],"dc:type.qualificationlevel":["Doctoral Thesis"],"dc:type.qualificationname":["Doctor of Philosophy"]},"updated_at":"2026-07-24T02:08:26Z"}