Overexpression of suppressor of cytokine signaling-1 impairs pre-T-cell receptor-induced proliferation but not differentiation of immature thymocytes.
Cytokines play an essential role during early T-cell development. However, the mechanisms controlling cytokine signaling in developing thymocytes have not been elucidated. Cytokine receptor signaling can be modulated by suppressor of cytokine signaling-1 (SOCS-1), which acts as a negative regulator of Janus kinases. SOCS-1 is normally expressed throughout thymocyte development; however, retroviral-mediated overexpression of SOCS-1 in fetal liver-derived hematopoietic progenitors prevented their progression beyond the earliest stage of T-cell development. Further analysis revealed that SOCS-1 expression is transiently suppressed following pre-T-cell receptor (TCR) signaling. Moreover, constitutive expression of SOCS-1 abrogated pre-TCR- mediated expansion of immature thymocytes but did not interfere with differentiation. These findings reveal that SOCS-1 serves to regulate cytokine signaling at critical checkpoints during early T-cell development.
Trop
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Departments of Immunology, Medicine, and Medical Biophysics, University of Toronto, Ontario, Canada.
De Sepulveda
P
P
Zúñiga-Pflücker
J C
JC
Rottapel
R
R
D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation; D002455:Cell Division; D019070:Cell Lineage; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D053631:Interleukin Receptor Common gamma Subunit; D015851:Interleukin-7 / Q000502:physiology; D008099:Liver / Q000196:embryology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D017434:Protein Structure, Tertiary; D016693:Receptors, Antigen, T-Cell, alpha-beta; D020395:Receptors, Interleukin-7 / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000502:physiology; D012097:Repressor Proteins; D015398:Signal Transduction; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000196:embryology
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C507942:Il2rg protein, mouse; D053631:Interleukin Receptor Common gamma Subunit; D015851:Interleukin-7; D008562:Membrane Glycoproteins; C499308:Rag2 protein, mouse; D016693:Receptors, Antigen, T-Cell, alpha-beta; D020395:Receptors, Interleukin-7; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; C064655:V(D)J recombination activating protein 2; C090377:pre-T cell receptor alpha