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Characterization of Ly108-H1 Signaling Reveals Ly108-3 Expression and Additional Strain-Specific Differences in Lupus Prone Mice
dc.contributor.author | Rietdijk, Svend | |
dc.contributor.author | Keszei, Marton | |
dc.contributor.author | Castro, Wilson | |
dc.contributor.author | Terhorst, Cox | |
dc.contributor.author | Abadía Molina, Ana Clara | |
dc.date.accessioned | 2023-04-14T08:55:10Z | |
dc.date.available | 2023-04-14T08:55:10Z | |
dc.date.issued | 2023-03-06 | |
dc.identifier.citation | Rietdijk, S.; Keszei, M.; Castro,W.; Terhorst, C.; Abadía-Molina, A.C. Characterization of Ly108-H1 Signaling Reveals Ly108-3 Expression and Additional Strain-Specific Differences in Lupus Prone Mice. Int. J. Mol. Sci. 2023, 24, 5024. [https://doi.org/10.3390/ijms24055024] | es_ES |
dc.identifier.uri | https://hdl.handle.net/10481/81045 | |
dc.description | Supplementary Materials: The following supporting information can be downloaded at: https:// www.mdpi.com/article/10.3390/ijms24055024/s1. References [58,59] are cited in the Supplementary Materials. | es_ES |
dc.description.abstract | Ly108 (SLAMF6) is a homophilic cell surface molecule that binds SLAM-associated protein (SAP), an intracellular adapter protein that modulates humoral immune responses. Furthermore, Ly108 is crucial for the development of natural killer T (NKT) cells and CTL cytotoxicity. Significant attention has been paid towards expression and function of Ly108 since multiple isoforms were identified, i.e., Ly108-1, Ly108-2, Ly108-3, and Ly108-H1, some of which are differentially expressed in several mouse strains. Surprisingly, Ly108-H1 appeared to protect against disease in a congenic mouse model of Lupus. Here, we use cell lines to further define Ly108-H1 function in comparison with other isoforms. We show that Ly108-H1 inhibits IL-2 production while having little effect upon cell death. With a refined method, we could detect phosphorylation of Ly108-H1 and show that SAP binding is retained. We propose that Ly108-H1 may regulate signaling at two levels by retaining the capability to bind its extracellular as well as intracellular ligands, possibly inhibiting downstream pathways. In addition, we detected Ly108-3 in primary cells and show that this isoform is also differentially expressed between mouse strains. The presence of additional binding motifs and a non-synonymous SNP in Ly108-3 further extends the diversity between murine strains. This work highlights the importance of isoform awareness, as inherent homology can present a challenge when interpreting mRNA and protein expression data, especially as alternatively splicing potentially affects function. | es_ES |
dc.description.sponsorship | Plan Estatal de Investigación Científica y Técnica y de Innovación, ISCIII. Subdirección, General de Evaluación y Fomento de la Investigación, Ministerio de Economía y Competitividad, Spain. (Grants PI16/01642) | es_ES |
dc.description.sponsorship | Grupo de Investigación de Biología e Inmunología Celular, BIO-225, Consejería de Universidad Investigación e Innovación, Junta de Andalucía, Spain. This work was supported by the following grants to C. Terhorst from the National Institutes of Health (DK073339 and AI-065687) | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | MDPI | es_ES |
dc.rights | Atribución 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | Ly108 | es_ES |
dc.subject | NTB-A | es_ES |
dc.subject | SLAMF6 | es_ES |
dc.subject | Isoforms | es_ES |
dc.subject | SAP | es_ES |
dc.subject | SLAM | es_ES |
dc.title | Characterization of Ly108-H1 Signaling Reveals Ly108-3 Expression and Additional Strain-Specific Differences in Lupus Prone Mice | es_ES |
dc.type | journal article | es_ES |
dc.rights.accessRights | open access | es_ES |
dc.identifier.doi | 10.3390/ijms24055024 | |
dc.type.hasVersion | VoR | es_ES |