The orphan adapter protein SLY1 as a novel anti-apoptotic protein required for thymocyte development.
BACKGROUND
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 SLY1Delta/Delta mice harbouring a partial deletion in the N-terminal region of SLY1 which revealed profound immunological defects in T and B cell functions.


RESULTS
In this study, T cell development in SLY1-/- and SLY1Delta/Delta 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.


CONCLUSIONS
Thus, our results suggest a non-redundant role for SLY1 in integrating signals from both receptors in early T cell progenitors in the thymus.
Reis
Bernhard
B
Institute of Medical Microbiology and Hospital Hygiene, Heinrich-Heine-University Duesseldorf, Universitaetsstrasse 1, D-40225 Duesseldorf, Germany. bernhard.reis@uni-duesseldorf.de
Pfeffer
Klaus
K
Beer-Hammer
Sandra
S
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D017209:Apoptosis; D015704:CD4 Antigens; D016827:CD8 Antigens; D002454:Cell Differentiation; D002460:Cell Line; D018507:Gene Expression Regulation, Developmental; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054504:Precursor Cells, T-Lymphoid / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology / Q000378:metabolism*; D051880:Receptors, Notch / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000254:growth & development / Q000276:immunology*
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D015704:CD4 Antigens; D016827:CD8 Antigens; D051034:Inhibitor of Apoptosis Proteins; D008562:Membrane Glycoproteins; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D051880:Receptors, Notch; C506091:SLY1 protein, mouse; C090377:pre-T cell receptor alpha