The orphan adapter protein SLY1 as a novel anti-apoptotic protein required for thymocyte development.

Publisher: BioMed Central Country of Publication: England NLM ID: 100966980 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2172 (Electronic) Linking ISSN: 14712172 NLM ISO Abbreviation: BMC Immunol Subsets: MEDLINE

Original Publication: London : BioMed Central, [2000-

Adaptor Proteins, Signal Transducing/*metabolism ; Inhibitor of Apoptosis Proteins/*metabolism ; Membrane Glycoproteins/*metabolism ; Precursor Cells, T-Lymphoid/*metabolism ; Receptors, Antigen, T-Cell, alpha-beta/*metabolism ; Thymus Gland/*immunology; Adaptor Proteins, Signal Transducing/genetics ; Adaptor Proteins, Signal Transducing/immunology ; Adaptor Proteins, Vesicular Transport ; Animals ; Apoptosis ; CD4 Antigens ; CD8 Antigens ; Cell Differentiation ; Cell Line ; Gene Expression Regulation, Developmental ; Inhibitor of Apoptosis Proteins/genetics ; Inhibitor of Apoptosis Proteins/immunology ; Lymphocyte Activation ; Membrane Glycoproteins/immunology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Precursor Cells, T-Lymphoid/cytology ; Precursor Cells, T-Lymphoid/immunology ; Receptors, Antigen, T-Cell/immunology ; Receptors, Antigen, T-Cell/metabolism ; Receptors, Antigen, T-Cell, alpha-beta/immunology ; Receptors, Notch/immunology ; Receptors, Notch/metabolism ; Signal Transduction/immunology ; T-Lymphocytes/cytology ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; Thymus Gland/cytology ; Thymus Gland/growth & 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.
Conclusion: Thus, our results suggest a non-redundant role for SLY1 in integrating signals from both receptors in early T cell progenitors in the thymus.

Immunity. 1994 May;1(2):83-93. (PMID: 7534200)
Nat Immunol. 2007 Feb;8(2):137-44. (PMID: 17242687)
Nat Immunol. 2005 Jul;6(7):663-70. (PMID: 15951813)
Oncogene. 2003 May 15;22(19):2972-83. (PMID: 12771949)
Biochem Biophys Res Commun. 2001 Oct 19;288(1):137-41. (PMID: 11594764)
Nat Immunol. 2005 Sep;6(9):881-8. (PMID: 16056227)
Nat Immunol. 2004 May;5(5):539-45. (PMID: 15077109)
J Immunol. 2004 May 1;172(9):5230-9. (PMID: 15100261)
Biochim Biophys Acta. 2001 Jul 30;1520(1):89-93. (PMID: 11470164)
Cell. 1993 May 7;73(3):513-9. (PMID: 8387894)
Br J Cancer. 2006 Nov 20;95(10):1419-23. (PMID: 17088907)
J Immunol. 2007 May 1;178(9):5443-53. (PMID: 17442925)
Cell Cycle. 2008 Apr 15;7(8):965-70. (PMID: 18414037)
Nat Immunol. 2004 Apr;5(4):410-7. (PMID: 15034575)
Immunity. 2002 Dec;17(6):749-56. (PMID: 12479821)
Mol Immunol. 2009 Feb;46(5):969-77. (PMID: 18950867)
J Immunol. 1994 May 15;152(10):4783-92. (PMID: 7513723)
Immunity. 1999 Sep;11(3):299-308. (PMID: 10514008)
Cell. 1992 Mar 6;68(5):869-77. (PMID: 1547488)
Annu Rev Cell Dev Biol. 2007;23:463-93. (PMID: 17506693)
Mol Cell Biol. 2005 Nov;25(21):9646-60. (PMID: 16227612)
Genes Dev. 2005 Sep 15;19(18):2199-211. (PMID: 16166381)
Biochim Biophys Acta. 1997 Oct 24;1333(2):F151-78. (PMID: 9395285)
Annu Rev Immunol. 2005;23:945-74. (PMID: 15771590)
J Biol Chem. 2003 Mar 14;278(11):9267-75. (PMID: 12515807)
J Exp Med. 2004 Sep 20;200(6):737-47. (PMID: 15381729)
EMBO J. 2007 Jul 25;26(14):3441-50. (PMID: 17599070)
Cancer Res. 1999 Apr 1;59(7 Suppl):1685s-1692s. (PMID: 10197581)
Cancer Res. 2003 Dec 1;63(23):8451-60. (PMID: 14679009)
Genes Chromosomes Cancer. 2008 Sep;47(9):810-8. (PMID: 18523997)
Curr Opin Immunol. 1999 Apr;11(2):135-42. (PMID: 10322152)
Oncogene. 2001 Aug 30;20(38):5373-7. (PMID: 11536050)
Nat Immunol. 2007 May;8(5):451-6. (PMID: 17440450)
Immunity. 1997 Nov;7(5):601-7. (PMID: 9390684)

0 (Adaptor Proteins, Signal Transducing)
0 (Adaptor Proteins, Vesicular Transport)
0 (CD4 Antigens)
0 (CD8 Antigens)
0 (Inhibitor of Apoptosis Proteins)
0 (Membrane Glycoproteins)
0 (Receptors, Antigen, T-Cell)
0 (Receptors, Antigen, T-Cell, alpha-beta)
0 (Receptors, Notch)
0 (SLY1 protein, mouse)
0 (pre-T cell receptor alpha)

Date Created: 20090717 Date Completed: 20091130 Latest Revision: 20211020

20240829

PMC2717057

10.1186/1471-2172-10-38

19604361