Delta-like 1-Lysine613 regulates notch signaling

Liguo Zhang, Ryan C. Widau, B. Paul Herring, Patricia J. Gallagher

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Delta ligands are important for regulating Notch signaling through transcellular stimulation of Notch receptors. The cytoplasmic tails of Delta ligands have multiple potential regulatory sites including several lysine residues that are putative targets for ubiquitination by the E3 ubiquitin ligases, Mind Bomb and Neuralized. To identify possible roles for specific lysine residues in the cytoplasmic tail of the Notch ligand Dll1 a mutational and functional analysis was performed. Examination of a panel of individual or clustered lysine mutants demonstrated that lysine 613 (K613) in the cytoplasmic tail of Dll1 is a key residue necessary for transcellular activation of Notch signaling. Multi-ubiquitination of the Dll1 mutant Dll1-K613R was altered compared to wild type Dll1, and the K613R mutation blocked the ability of Dll1 to interact with Notch1. Finally, mutation of K613 did not affect the stability of Dll1 or its ability to traffic to recycle to the plasma membrane, but did enhance the fraction associated with lipid rafts. Collectively these results suggest that the transcellular defect in Notch signaling attributed to residue K613 in cytoplasmic tail of Dll1 may result from altering its multi-ubiquitination and increasing its retention in lipid rafts.

Original languageEnglish (US)
Pages (from-to)2036-2043
Number of pages8
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1813
Issue number12
DOIs
StatePublished - Dec 1 2011

Keywords

  • Delta
  • Endocytosis
  • Lipid raft microdomain
  • Notch
  • Recycling
  • Ubiquitin

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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