The orphan adapter protein SLY1 as a novel anti-apoptotic protein required for thymocyte development
1 Institute of Medical Microbiology and Hospital Hygiene, Heinrich-Heine-University Duesseldorf, Universitaetsstrasse 1, D-40225 Duesseldorf, Germany
2 Institute of Experimental and Clinical Pharmacology and Toxicology, Eberhard-Karls-University Tuebingen, Wilhelmstrasse 56, D-72074 Tuebingen, Germany
BMC Immunology 2009, 10:38 doi:10.1186/1471-2172-10-38Published: 15 July 2009
SH3 containing Lymphocyte Protein (SLY1) is a putative adapter protein exclusively expressed in lymphocytes which is involved in antigen receptor induced activation. We previously have generated SLY1Δ/Δ mice harbouring a partial deletion in the N-terminal region of SLY1 which revealed profound immunological defects in T and B cell functions.
In this study, T cell development in SLY1-/- and SLY1Δ/Δ mice was analysed ex vivo and upon cultivation with the bone marrow stromal cell line OP9. SLY1-deficient thymocytes were compromised in inducing nutrient receptor expression and ribosomal protein S6 phosphorylation, indicating a defect in mTOR complex activation. Furthermore, SLY1 was identified as a novel anti-apoptotic protein required for developmental progression of T cell precursors to the CD4+CD8+ double-positive stage by protecting from premature programmed cell death initiation in developing CD4-CD8- double-negative thymocytes. In addition, SLY1 phosphorylation was differentially regulated upon Notch ligand-mediated stimulation and expression of the preTCR.
Thus, our results suggest a non-redundant role for SLY1 in integrating signals from both receptors in early T cell progenitors in the thymus.