Journal
JOURNAL OF IMMUNOLOGY
Volume 168, Issue 4, Pages 1649-1658Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.168.4.1649
Keywords
-
Categories
Funding
- NCI NIH HHS [CA73656, P01CA06927, CA87407] Funding Source: Medline
Ask authors/readers for more resources
Progression of immature CD4(-)CD8(-) thymocytes beyond tire beta-selection checkpoint to the CD4(+)CD8(+) stage requires activation of the pre-TCR complex; however, few of the DNA-binding proteins that serve as molecular effectors of those pre-TCR signals have been identified. We demonstrate in this study that members of the early growth response (Egr) family of transcription factors are critical effectors of tire signals that promote this developmental transition. Specifically, the induction of three Egr family members (Egr1, 2, and 3) correlates witty pre-TCR activation and development of CD4(-)CD8(-) thymocytes beyond the beta-selection checkpoint. Enforced expression of each of these Egr factors is able to bypass the block in thymocyte development associated with defective pre-TCR function. However, Egr fancily members pray play somewhat distinct roles in promoting thymocyte development, because there are differences in the genes modulated by enforced expression of particular Egr factors. Finally, interfering with Egr function using dominant-negative proteins disrupts thymocyte development from the CD4(-)CD8(-) to the CD4(+)CD8(+) stage. Taken together, these data demonstrate that the Egr proteins play an essential role in executing the differentiation program initiated by pre-TCR signaling.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available