@misc{10481/81045,
year = {2023},
month = {3},
url = {https://hdl.handle.net/10481/81045},
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.},
organization = {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)},
organization = {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)},
publisher = {MDPI},
keywords = {Ly108},
keywords = {NTB-A},
keywords = {SLAMF6},
keywords = {Isoforms},
keywords = {SAP},
keywords = {SLAM},
title = {Characterization of Ly108-H1 Signaling Reveals Ly108-3 Expression and Additional Strain-Specific Differences in Lupus Prone Mice},
doi = {10.3390/ijms24055024},
author = {Rietdijk, Svend and Keszei, Marton and Castro, Wilson and Terhorst, Cox and Abadía Molina, Ana Clara},
}