title: CD5-CK2 Signaling Modulates Erk Activation and Thymocyte Survival.
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.
authors.affiliation: Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México, México.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Mier-Aguilar
authors.affiliation: Division of Clinical Immunology and Rheumatology, Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, United States of America.
authors.forename: Kevin S
authors.initials: KS
authors.lastname: Cashman
authors.affiliation: Division of Clinical Immunology and Rheumatology, Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, United States of America.|Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States of America.
authors.forename: Chander
authors.initials: C
authors.lastname: Raman
authors.affiliation: Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México, México.
authors.forename: Gloria
authors.initials: G
authors.lastname: Soldevila
mesh_terms: D000818:Animals; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018956:CD5 Antigens / Q000378:metabolism*; D047390:Casein Kinase II / Q000378:metabolism*; D002470:Cell Survival; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D015398:Signal Transduction; D060168:Thymocytes / Q000166:cytology*
chemical_list: D018956:CD5 Antigens; D047390:Casein Kinase II; D048049:Extracellular Signal-Regulated MAP Kinases