ArticleThe Journal of cell biology1997
Apical enrichment of human EGF precursor in Madin-Darby canine kidney cells involves preferential basolateral ectodomain cleavage sensitive to a metalloprotease inhibitor.
Article in The Journal of cell biology, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 89 citations in OpenAlex.
- Impaired basolateral sorting of pro-EGF causes isolated recessive renal hypomagnesemia.The Journal of clinical investigation · 2007Trial
- Urinary EGF Reflects Distal Tubular Mass and Is Associated with Hypertension, Serum Magnesium, and Kidney Outcomes.Kidney360 · 2025Article
- Induction of apically mistrafficked epiregulin disrupts epithelial polarity via aberrant EGFR signaling.Journal of cell science · 2021Article
- The Crossroads between Zinc and Steroidal Implant-Induced Growth of Beef Cattle.Animals : an open access journal from MDPI · 2021Review
- Autocrine Signaling in Cardiac Remodeling: A Rich Source of Therapeutic Targets.Journal of the American Heart Association · 2021Review
- Polarized epidermal growth factor secretion ensures robust vulval cell fate specification inDevelopment (Cambridge, England) · 2020Article
- The role of epidermal growth factor receptor (EGFR) signaling in SARS coronavirus-induced pulmonary fibrosis.Antiviral research · 2017Review
- Induction of lateral lumens through disruption of a monoleucine-based basolateral-sorting motif in betacellulin.Journal of cell science · 2015Article
- Heterotrimeric G proteins directly regulate MMP14/membrane type-1 matrix metalloprotease: a novel mechanism for GPCR-EGFR transactivation.The Journal of biological chemistry · 2015Article
- EGFR controls IQGAP basolateral membrane localization and mitotic spindle orientation during epithelial morphogenesis.The EMBO journal · 2014Article
- Trafficking of epidermal growth factor receptor ligands in polarized epithelial cells.Annual review of physiology · 2014Review
- Regulation of receptor tyrosine kinase ligand processing.Cold Spring Harbor perspectives in biology · 2014Article
- EGF shifts human airway basal cell fate toward a smoking-associated airway epithelial phenotype.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Transformation of polarized epithelial cells by apical mistrafficking of epiregulin.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Identification of a novel mono-leucine basolateral sorting motif within the cytoplasmic domain of amphiregulin.Traffic (Copenhagen, Denmark) · 2011Article
- Mammalian EGF receptor activation by the rhomboid protease RHBDL2.EMBO reports · 2011Article
- Sequential and gamma-secretase-dependent processing of the betacellulin precursor generates a palmitoylated intracellular-domain fragment that inhibits cell growth.Journal of cell science · 2010Article
- Molecular and cellular mechanisms of ectodomain shedding.Anatomical record (Hoboken, N.J. : 2007) · 2010Review
- Inherited forms of renal hypomagnesemia: an update.Pediatric nephrology (Berlin, Germany) · 2009Review
- The role of protease activity in ErbB biology.Experimental cell research · 2009Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
EGF precursor (proEGF) is a member of the family of membrane-anchored EGF-like growth factors that bind with high affinity to the epidermal growth factor receptor (EGFR). In contrast to human transforming growth factor-alpha precursor (proTGFalpha), which is sorted basolaterally in Madin-Darby canine kidney (MDCK) cells (Dempsey, P., and R. Coffey, 1994. J. Biol. Chem. 269:16878-16889), we now demonstrate that human proEGF overexpressed in MDCK cells is found predominantly at the apical membrane domain under steady-state conditions. Nascent proEGF (185 kD) is not sorted but is delivered equally to the apical and basolateral membranes, where it is proteolytically cleaved within its ectodomain to release a soluble 170-kD EGF form into the medium. Unlike the fate of TGFalpha in MDCK cells, the soluble 170-kD EGF species accumulates in the medium, does not interact with the EGFR, and is not processed to the mature 6-kD peptide. We show that the rate of ectodomain cleavage of 185-kD proEGF is fourfold greater at the basolateral surface than at the apical surface and is sensitive to a metalloprotease inhibitor, batimastat. Batimastat dramatically inhibited the release of soluble 170-kD EGF into the apical and basal medium by 7 and 60%, respectively, and caused a concordant increase in the expression of 185-kD proEGF at the apical and basolateral cell surfaces of 150 and 280%, respectively. We propose that preferential ectodomain cleavage at the basolateral surface contributes to apical domain localization of 185-kD proEGF in MDCK cells, and this provides a novel mechanism to achieve a polarized distribution of cell surface membrane proteins under steady-state conditions. In addition, differences in disposition of EGF and TGFalpha in polarized epithelial cells offer a new conceptual framework to consider the actions of these polypeptide growth factors.
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Registered trials
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.