First Author | Costello PS | Year | 2004 |
Journal | Nat Immunol | Volume | 5 |
Issue | 3 | Pages | 289-98 |
PubMed ID | 14770179 | Mgi Jnum | J:88515 |
Mgi Id | MGI:3033573 | Doi | 10.1038/ni1038 |
Citation | Costello PS, et al. (2004) Ternary complex factor SAP-1 is required for Erk-mediated thymocyte positive selection. Nat Immunol 5(3):289-98 |
abstractText | Thymocyte selection and differentiation requires extracellular signal-regulated kinase (Erk) signaling, but transcription factor substrates of Erk in thymocytes are unknown. We have characterized the function of SAP-1 (Elk4), an Erk-regulated transcription factor, in thymocyte development. Early thymocyte development was normal, but single-positive thymocyte and peripheral T cell numbers were reduced, reflecting a T cell-autonomous defect. T cell receptor-induced activation of SAP-1 target genes such as Egr1 was substantially impaired in double-positive thymocytes, although Erk activation was normal. Analysis of T cell receptor transgenes showed that positive selection was reduced by 80-90% in SAP-1-deficient mice; heterozygous mice showed a moderate defect. Negative selection was unimpaired. SAP-1 thus directly links Erk signaling to the transcriptional events required for thymocyte positive selection. |