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• W2163531148 abstract "A novel mode of crosstalk between the EGFR-Ras-MAPK and LIN-12/Notch pathways occurs during the patterning of a row of vulval precursor cells (VPCs) in Caenorhabditis elegans: activation of the EGFR-Ras-MAPK pathway in the central VPC promotes endocytosis and degradation of LIN-12 protein. LIN-12 downregulation in the central VPC is a prerequisite for the activity of the lateral signal, which activates LIN-12 in neighboring VPCs. Here we characterize cis-acting targeting sequences in the LIN-12 intracellular domain and find that in addition to a di-leucine motif, serine/threonine residues are important for internalization and lysine residues are important for post-internalization trafficking and degradation. We also identify two trans-acting factors that are required for post-internalization trafficking and degradation: ALX-1, a homolog of yeast Bro1p and mammalian Alix and the WWP-1/Su(dx)/Itch ubiquitin ligase. By examining the effects of mutated forms of LIN-12 and reduced wwp-1 or alx-1 activity on subcellular localization and activity of LIN-12, we provide evidence that the lateral signal-inhibiting activity of LIN-12 resides in the extracellular domain and occurs at the apical surface of the VPCs." @default.
• W2163531148 created "2016-06-24" @default.
• W2163531148 creator A5057192752 @default.
• W2163531148 creator A5069328543 @default.
• W2163531148 date "2005-11-15" @default.
• W2163531148 modified "2023-10-14" @default.
• W2163531148 title "LIN-12/Notch trafficking and regulation of DSL ligand activity during vulval induction in<i>Caenorhabditis elegans</i>" @default.
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• W2163531148 doi "https://doi.org/10.1242/dev.02076" @default.
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