title: Characterization of Ly108 in the thymus: evidence for distinct properties of a novel form of Ly108.
abstract: Ly108 (CD352) is a member of the signaling lymphocyte activation molecule (SLAM) family of receptors that signals through SLAM-associated protein (SAP), an SH2 domain protein that can function by the recruitment of Src family kinases or by competition with phosphatases. Ly108 is expressed on a variety of hematopoietic cells, with especially high levels on developing thymocytes. We find that Ly108 is constitutively tyrosine phosphorylated in murine thymi in a SAP- and Fyn kinase-dependent manner. Phosphorylation of Ly108 is rapidly lost after thymocyte disaggregation, suggesting dynamic contact-mediated regulation of Ly108. Similar to recent reports, we find at least three isoforms of Ly108 mRNA and protein in the thymus, which are differentially expressed in the thymi of C57BL/6 and 129S6 mice that express the lupus-resistant and lupus-prone haplotypes of Ly108, respectively. Notably, the recently described novel isoform Ly108-H1 is not expressed in mice having the lupus-prone haplotype of Ly108, but is expressed in C57BL/6 mice. We further provide evidence for differential phosphorylation of these isoforms; the novel Ly108-H1does not undergo tyrosine phosphorylation, suggesting that it functions as a decoy isoform that contributes to the reduced overall phosphorylation of Ly108 seen in C57BL/6 mice. Our study suggests that Ly108 is dynamically regulated in the thymus, shedding light on Ly108 isoform expression and phosphorylation.
authors.affiliation: Institute of Biomedical Sciences, The George Washington University, Washington, DC 20052, USA.
authors.forename: Mala
authors.initials: M
authors.lastname: Dutta
authors.forename: Pamela L
authors.initials: PL
authors.lastname: Schwartzberg
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000950:Antigens, Ly / Q000737:chemistry / Q000502:physiology*; D002450:Cell Communication; D016384:Consensus Sequence; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000032:analysis; D020033:Protein Isoforms / Q000737:chemistry / Q000502:physiology; D011499:Protein Processing, Post-Translational; D051076:Proto-Oncogene Proteins c-fyn / Q000378:metabolism; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D060168:Thymocytes / Q000166:cytology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism*; D000071176:Signaling Lymphocytic Activation Molecule Family
chemical_list: D000950:Antigens, Ly; D047908:Intracellular Signaling Peptides and Proteins; D019000:Phosphotyrosine; D020033:Protein Isoforms; D051076:Proto-Oncogene Proteins c-fyn; D012333:RNA, Messenger; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; C499569:Sh2d1a protein, mouse; C494960:Fyn protein, mouse; C000604063:Slamf6 protein, mouse; D000071176:Signaling Lymphocytic Activation Molecule Family