ADAM10 is essential for proteolytic activation of Notch during thymocyte development.

Published

Journal Article

Notch signaling pathway has been shown to play essential roles in T lymphocyte development. Activation of Notch requires a sequential proteolytic cleavage, which converts Notch from the full-length membrane-bound form to a transcriptionally active intracellular fragment. Studies in Drosophila showed that Kuzbanian (Kuz) is responsible for the enzymatic cleavage of extracellular S2 site upon Notch binding to its ligand Delta. Both a disintegrin and metalloprotease (ADAM) 10 and ADAM17, members of the ADAM family metalloproteases, have been indicated as the mammalian counterpart of Kuz in activating Notch in mammals. Here, we investigated functions of ADAM10 in Notch signaling during thymocyte development. We show that conditional disruption of the Adam10 gene in mouse thymocytes results in a developmental defect similar to the phenotypes previously described for T lineage-specific disruption of Notch1. We further show that the activation of Notch1 and its downstream target genes Deltex-1 and Pre-Ta are impaired in Adam10-deficient thymocytes. Our study demonstrates a T cell intrinsic role for Adam10 in activation of Notch1 during thymocyte development.

Full Text

Duke Authors

Cited Authors

  • Tian, L; Wu, X; Chi, C; Han, M; Xu, T; Zhuang, Y

Published Date

  • September 2008

Published In

Volume / Issue

  • 20 / 9

Start / End Page

  • 1181 - 1187

PubMed ID

  • 18635581

Pubmed Central ID

  • 18635581

Electronic International Standard Serial Number (EISSN)

  • 1460-2377

Digital Object Identifier (DOI)

  • 10.1093/intimm/dxn076

Language

  • eng

Conference Location

  • England