CD5-CK2 Signaling Modulates Erk Activation and Thymocyte Survival
CD5 is well recognized for its importance in thymic selection. Although this property of CD5 has been attributed to its ITIM-domain dependent regulation of TCR-signal strength, the mechanism has not been established. A second major signaling domain within the cytoplasmic tail of CD5 is a CK2 binding...
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| creator | Mier-Aguilar, Carlos A Cashman, Kevin S Raman, Chander Soldevila, Gloria |
| description | CD5 is well recognized for its importance in thymic selection. Although this property of CD5 has been attributed to its ITIM-domain dependent regulation of TCR-signal strength, the mechanism has not been established. A second major signaling domain within the cytoplasmic tail of CD5 is a CK2 binding/activation domain (CD5-CK2BD). Using a gene-targeted mouse in which the CD5-CK2BD is selectively ablated (CD5-ΔCK2BD), we determined that loss of function of CD5-CK2 signaling in a MHC-II selecting TCR transgenic (OT-II) mouse resulted in decrease in double positive (DP) thymocytes, which correlated with enhanced apoptosis. Remarkably, DP cells expressing high levels of CD5 and CD69 and single positive (CD4+SP) thymocytes were increased in CD5-ΔCK2BD mice indicating that CD5-CK2 signaling regulates positive selection and promotes survival. Consistent with this possibility, we determined that the activation and nuclear localization of ERK as well as apoptosis was greater in thymic populations from OTII CD5-ΔCK2BD mice than OTII CD5-WT mice following injection of OVA323-339-peptide. The mobilization of Ca2+, an early event of TCR activation, was not altered by the loss of CD5-CK2 signaling. Collectively, these data demonstrate that the CD5-CK2 signaling axis regulates positive selection by modulating activation of ERK and promoting survival independent of proximal TCR signals. |
| doi_str_mv | 10.1371/journal.pone.0168155 |
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Although this property of CD5 has been attributed to its ITIM-domain dependent regulation of TCR-signal strength, the mechanism has not been established. A second major signaling domain within the cytoplasmic tail of CD5 is a CK2 binding/activation domain (CD5-CK2BD). Using a gene-targeted mouse in which the CD5-CK2BD is selectively ablated (CD5-ΔCK2BD), we determined that loss of function of CD5-CK2 signaling in a MHC-II selecting TCR transgenic (OT-II) mouse resulted in decrease in double positive (DP) thymocytes, which correlated with enhanced apoptosis. Remarkably, DP cells expressing high levels of CD5 and CD69 and single positive (CD4+SP) thymocytes were increased in CD5-ΔCK2BD mice indicating that CD5-CK2 signaling regulates positive selection and promotes survival. Consistent with this possibility, we determined that the activation and nuclear localization of ERK as well as apoptosis was greater in thymic populations from OTII CD5-ΔCK2BD mice than OTII CD5-WT mice following injection of OVA323-339-peptide. The mobilization of Ca2+, an early event of TCR activation, was not altered by the loss of CD5-CK2 signaling. Collectively, these data demonstrate that the CD5-CK2 signaling axis regulates positive selection by modulating activation of ERK and promoting survival independent of proximal TCR signals.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0168155</identifier><identifier>PMID: 28030587</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Activation ; Animals ; Apoptosis ; Biology and Life Sciences ; Casein Kinase II - metabolism ; CD4 antigen ; CD4-Positive T-Lymphocytes - cytology ; CD4-Positive T-Lymphocytes - immunology ; CD4-Positive T-Lymphocytes - metabolism ; CD5 antigen ; CD5 Antigens - metabolism ; CD69 antigen ; Cell cycle ; Cell Survival ; Clonal selection ; Enzyme Activation ; Extracellular signal-regulated kinase ; Extracellular Signal-Regulated MAP Kinases - metabolism ; Immunology ; Kinases ; Ligands ; Localization ; Lymphocyte Activation ; Lymphocytes ; Major histocompatibility complex ; Medical research ; Medicine and Health Sciences ; Mice ; Mice, Inbred C57BL ; Phosphorylation ; Positive selection ; Proteins ; Rheumatology ; Signal strength ; Signal Transduction ; Signaling ; Survival ; T cell receptors ; T cells ; T-cell receptor ; Thymocytes ; Thymocytes - cytology ; Thymus</subject><ispartof>PloS one, 2016-12, Vol.11 (12), p.e0168155-e0168155</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Mier-Aguilar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2016 Mier-Aguilar et al 2016 Mier-Aguilar et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c791t-7ce6951a82a16eea244711c5e3ad002ad21926c980139fac3839653bce8a8f833</citedby><cites>FETCH-LOGICAL-c791t-7ce6951a82a16eea244711c5e3ad002ad21926c980139fac3839653bce8a8f833</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5193405/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5193405/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53769,53771,79346,79347</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28030587$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Baldwin, Troy A.</contributor><creatorcontrib>Mier-Aguilar, Carlos A</creatorcontrib><creatorcontrib>Cashman, Kevin S</creatorcontrib><creatorcontrib>Raman, Chander</creatorcontrib><creatorcontrib>Soldevila, Gloria</creatorcontrib><title>CD5-CK2 Signaling Modulates Erk Activation and Thymocyte Survival</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>CD5 is well recognized for its importance in thymic selection. Although this property of CD5 has been attributed to its ITIM-domain dependent regulation of TCR-signal strength, the mechanism has not been established. A second major signaling domain within the cytoplasmic tail of CD5 is a CK2 binding/activation domain (CD5-CK2BD). Using a gene-targeted mouse in which the CD5-CK2BD is selectively ablated (CD5-ΔCK2BD), we determined that loss of function of CD5-CK2 signaling in a MHC-II selecting TCR transgenic (OT-II) mouse resulted in decrease in double positive (DP) thymocytes, which correlated with enhanced apoptosis. Remarkably, DP cells expressing high levels of CD5 and CD69 and single positive (CD4+SP) thymocytes were increased in CD5-ΔCK2BD mice indicating that CD5-CK2 signaling regulates positive selection and promotes survival. Consistent with this possibility, we determined that the activation and nuclear localization of ERK as well as apoptosis was greater in thymic populations from OTII CD5-ΔCK2BD mice than OTII CD5-WT mice following injection of OVA323-339-peptide. The mobilization of Ca2+, an early event of TCR activation, was not altered by the loss of CD5-CK2 signaling. Collectively, these data demonstrate that the CD5-CK2 signaling axis regulates positive selection by modulating activation of ERK and promoting survival independent of proximal TCR signals.</description><subject>Activation</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Biology and Life Sciences</subject><subject>Casein Kinase II - metabolism</subject><subject>CD4 antigen</subject><subject>CD4-Positive T-Lymphocytes - cytology</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>CD4-Positive T-Lymphocytes - metabolism</subject><subject>CD5 antigen</subject><subject>CD5 Antigens - metabolism</subject><subject>CD69 antigen</subject><subject>Cell cycle</subject><subject>Cell Survival</subject><subject>Clonal selection</subject><subject>Enzyme Activation</subject><subject>Extracellular signal-regulated kinase</subject><subject>Extracellular Signal-Regulated MAP Kinases - metabolism</subject><subject>Immunology</subject><subject>Kinases</subject><subject>Ligands</subject><subject>Localization</subject><subject>Lymphocyte Activation</subject><subject>Lymphocytes</subject><subject>Major histocompatibility complex</subject><subject>Medical research</subject><subject>Medicine and Health Sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Phosphorylation</subject><subject>Positive selection</subject><subject>Proteins</subject><subject>Rheumatology</subject><subject>Signal strength</subject><subject>Signal Transduction</subject><subject>Signaling</subject><subject>Survival</subject><subject>T cell receptors</subject><subject>T cells</subject><subject>T-cell receptor</subject><subject>Thymocytes</subject><subject>Thymocytes - 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metabolism</topic><topic>CD4 antigen</topic><topic>CD4-Positive T-Lymphocytes - cytology</topic><topic>CD4-Positive T-Lymphocytes - immunology</topic><topic>CD4-Positive T-Lymphocytes - metabolism</topic><topic>CD5 antigen</topic><topic>CD5 Antigens - metabolism</topic><topic>CD69 antigen</topic><topic>Cell cycle</topic><topic>Cell Survival</topic><topic>Clonal selection</topic><topic>Enzyme Activation</topic><topic>Extracellular signal-regulated kinase</topic><topic>Extracellular Signal-Regulated MAP Kinases - metabolism</topic><topic>Immunology</topic><topic>Kinases</topic><topic>Ligands</topic><topic>Localization</topic><topic>Lymphocyte Activation</topic><topic>Lymphocytes</topic><topic>Major histocompatibility complex</topic><topic>Medical research</topic><topic>Medicine and Health Sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Phosphorylation</topic><topic>Positive selection</topic><topic>Proteins</topic><topic>Rheumatology</topic><topic>Signal strength</topic><topic>Signal Transduction</topic><topic>Signaling</topic><topic>Survival</topic><topic>T cell receptors</topic><topic>T cells</topic><topic>T-cell receptor</topic><topic>Thymocytes</topic><topic>Thymocytes - cytology</topic><topic>Thymus</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mier-Aguilar, Carlos A</creatorcontrib><creatorcontrib>Cashman, Kevin S</creatorcontrib><creatorcontrib>Raman, Chander</creatorcontrib><creatorcontrib>Soldevila, Gloria</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mier-Aguilar, Carlos A</au><au>Cashman, Kevin S</au><au>Raman, Chander</au><au>Soldevila, Gloria</au><au>Baldwin, Troy A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CD5-CK2 Signaling Modulates Erk Activation and Thymocyte Survival</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2016-12-28</date><risdate>2016</risdate><volume>11</volume><issue>12</issue><spage>e0168155</spage><epage>e0168155</epage><pages>e0168155-e0168155</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>CD5 is well recognized for its importance in thymic selection. Although this property of CD5 has been attributed to its ITIM-domain dependent regulation of TCR-signal strength, the mechanism has not been established. A second major signaling domain within the cytoplasmic tail of CD5 is a CK2 binding/activation domain (CD5-CK2BD). Using a gene-targeted mouse in which the CD5-CK2BD is selectively ablated (CD5-ΔCK2BD), we determined that loss of function of CD5-CK2 signaling in a MHC-II selecting TCR transgenic (OT-II) mouse resulted in decrease in double positive (DP) thymocytes, which correlated with enhanced apoptosis. Remarkably, DP cells expressing high levels of CD5 and CD69 and single positive (CD4+SP) thymocytes were increased in CD5-ΔCK2BD mice indicating that CD5-CK2 signaling regulates positive selection and promotes survival. Consistent with this possibility, we determined that the activation and nuclear localization of ERK as well as apoptosis was greater in thymic populations from OTII CD5-ΔCK2BD mice than OTII CD5-WT mice following injection of OVA323-339-peptide. The mobilization of Ca2+, an early event of TCR activation, was not altered by the loss of CD5-CK2 signaling. Collectively, these data demonstrate that the CD5-CK2 signaling axis regulates positive selection by modulating activation of ERK and promoting survival independent of proximal TCR signals.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28030587</pmid><doi>10.1371/journal.pone.0168155</doi><tpages>e0168155</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Activation Animals Apoptosis Biology and Life Sciences Casein Kinase II - metabolism CD4 antigen CD4-Positive T-Lymphocytes - cytology CD4-Positive T-Lymphocytes - immunology CD4-Positive T-Lymphocytes - metabolism CD5 antigen CD5 Antigens - metabolism CD69 antigen Cell cycle Cell Survival Clonal selection Enzyme Activation Extracellular signal-regulated kinase Extracellular Signal-Regulated MAP Kinases - metabolism Immunology Kinases Ligands Localization Lymphocyte Activation Lymphocytes Major histocompatibility complex Medical research Medicine and Health Sciences Mice Mice, Inbred C57BL Phosphorylation Positive selection Proteins Rheumatology Signal strength Signal Transduction Signaling Survival T cell receptors T cells T-cell receptor Thymocytes Thymocytes - cytology Thymus |
| title | CD5-CK2 Signaling Modulates Erk Activation and Thymocyte Survival |
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