ArticleProceedings of the National Academy of Sciences of the United States of America2004
Myristoylated Naked2 escorts transforming growth factor alpha to the basolateral plasma membrane of polarized epithelial cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 73 citations in OpenAlex.
- Dual blockade of the EGFR and COX-2 pathways: a phase II trial of cetuximab and celecoxib in patients with chemotherapy refractory metastatic colorectal cancer.American journal of clinical oncology · 2011Trial
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- Protein lipidation in health and disease: molecular basis, physiological function and pathological implication.Signal transduction and targeted therapy · 2024Review
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- Ubiquitin-independent proteasomal degradation driven by C-degron pathways.Molecular cell · 2023Article
- Recent Advances in the Study of Extracellular Vesicles in Colorectal Cancer.Gastroenterology · 2022Review
- Protein Myristoylation Plays a Role in the Nuclear Entry of the Parvovirus Minute Virus of Mice.Journal of virology · 2022Article
- NKD2 mediates stimulation-dependent ORAI1 trafficking to augment CaCell reports · 2021Article
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- The protein secretion modulator TMED9 drives CNIH4/TGFα/GLI signaling opposing TMED3-WNT-TCF to promote colon cancer metastases.Oncogene · 2019Article
- Protein kinase A-mediated phosphorylation of naked cuticle homolog 2 stimulates cell-surface delivery of transforming growth factor-α for epidermal growth factor receptor transactivation.Traffic (Copenhagen, Denmark) · 2019Article
- Nkd2 promotes the differentiation of dental follicle stem/progenitor cells into osteoblasts.International journal of molecular medicine · 2018Article
- Whole proteome analysis of human tankyrase knockout cells reveals targets of tankyrase-mediated degradation.Nature communications · 2017Article
- Directional Fluid Transport across Organ-Blood Barriers: Physiology and Cell Biology.Cold Spring Harbor perspectives in biology · 2017Review
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- EGF receptor ligands: recent advances.F1000Research · 2016Review
- TET-catalyzed 5-hydroxymethylcytosine regulates gene expression in differentiating colonocytes and colon cancer.Scientific reports · 2015Article
- Silencing NKD2 by promoter region hypermethylation promotes gastric cancer invasion and metastasis by up-regulating SOX18 in human gastric cancer.Oncotarget · 2015Article
- NKD2, a negative regulator of Wnt signaling, suppresses tumor growth and metastasis in osteosarcoma.Oncogene · 2015Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The epidermal growth factor receptor ligands transforming growth factor alpha (TGF alpha) and amphiregulin are delivered to the basolateral surface of polarized epithelial cells where they are cleaved by TACE/ADAM17. Basolateral sorting information resides in their cytoplasmic tail domains, but tail-interacting proteins required for basolateral trafficking have not been identified. Naked (NKD)1 and NKD2 are mammalian homologs of Drosophila Naked Cuticle, which negatively regulates canonical Wnt signaling by binding Dishevelled. We present evidence that NKD2, but not NKD1, binds to basolateral sorting motifs in the cytoplasmic tail of TGF alpha. Processing and cell-surface delivery of TGF alpha are accelerated in NKD2-overexpressing Madin-Darby canine kidney cells. NKD2 is myristoylated on glycine, the second residue. On expression of myristoylation-defective (G2A) NKD2, neither NKD2 nor TGF alpha appears at the basolateral plasma membrane of polarized Madin-Darby canine kidney cells; however, membrane staining for TGF alpha is restored on silencing expression of this mutant NKD2. Amphiregulin does not interact with NKD2 and retains its basolateral localization in G2A-NKD2-expressing cells, as do Na(+), K(+) ATPase alpha 1 and E-cadherin. These data identify an unexpected function for NKD2, i.e., myristoylation-dependent escort of TGF alpha to the basolateral plasma membrane of polarized epithelial cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.