ArticleMolecular biology of the cell2004
Autocrine extracellular signal-regulated kinase (ERK) activation in normal human keratinocytes: metalloproteinase-mediated release of amphiregulin triggers signaling from ErbB1 to ERK.
Article in Molecular biology of the cell, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 50 citations in OpenAlex.
- Amphiregulin Exerts Proangiogenic Effects in Developing Murine Lungs.Antioxidants (Basel, Switzerland) · 2024Article
- ADAM17-dependent signaling is required for oncogenic human papillomavirus entry platform assembly.eLife · 2019Article
- Amphiregulin Regulates Phagocytosis-Induced Cell Death in Monocytes via EGFR and the Bcl-2 Protein Family.Mediators of inflammation · 2019Article
- Article
- Membrane-Tethered Intracellular Domain of Amphiregulin Promotes Keratinocyte Proliferation.The Journal of investigative dermatology · 2016Article
- FAK activity is required for HGF to suppress TGF-β1-induced cellular proliferation.In vitro cellular & developmental biology. Animal · 2015Article
- Galectin-3 regulates intracellular trafficking of EGFR through Alix and promotes keratinocyte migration.The Journal of investigative dermatology · 2012Article
- Essential roles for soluble virion-associated heparan sulfonated proteoglycans and growth factors in human papillomavirus infections.PLoS pathogens · 2012Article
- Knock-down of amphiregulin inhibits cellular invasion in inflammatory breast cancer.Journal of cellular physiology · 2011Article
- Distinct activation of epidermal growth factor receptor by UTP contributes to epithelial cell wound repair.The American journal of pathology · 2011Article
- Protein secretion in human mammary epithelial cells following HER1 receptor activation: influence of HER2 and HER3 expression.BMC cancer · 2011Article
- TbetaRI/Alk5-independent TbetaRII signaling to ERK1/2 in human skin cells according to distinct levels of TbetaRII expression.Journal of cell science · 2011Article
- Amphiregulin carboxy-terminal domain is required for autocrine keratinocyte growth.The Journal of investigative dermatology · 2010Article
- A novel signaling pathway of tissue kallikrein in promoting keratinocyte migration: activation of proteinase-activated receptor 1 and epidermal growth factor receptor.Experimental cell research · 2010Article
- Metalloproteinase-mediated, context-dependent function of amphiregulin and HB-EGF in human keratinocytes and skin.The Journal of investigative dermatology · 2010Article
- Amphiregulin as a novel target for breast cancer therapy.Journal of mammary gland biology and neoplasia · 2008Review
- Agent based modelling helps in understanding the rules by which fibroblasts support keratinocyte colony formation.PloS one · 2008Article
- EGF and amphiregulin differentially regulate Cbl recruitment to endosomes and EGF receptor fate.The Biochemical journal · 2008Article
- Differential ErbB1 signaling in squamous cell versus basal cell carcinoma of the skin.The American journal of pathology · 2007Article
- HPV16 E6-mediated stabilization of ErbB2 in neoplastic transformation of human cervical keratinocytes.Oncogene · 2007Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
ErbB signaling through extracellular signal-regulated kinase (ERK) has been implicated in regulating the expression of ErbB ligands in hyperproliferative skin disorders and wound healing. Here, we characterize the process of autocrine ERK activation in cultured normal human keratinocytes (NHKs) subjected to growth factor (GF) deprivation. Basal ERK phosphorylation was lower after 48 h than after 24 h of GF deprivation, and lowest at 30-60 min after an additional medium change. ERK phosphorylation was markedly increased by low concentrations of epidermal growth factor (EGF) (0.2-1 ng/ml) that provoked only a limited increase in ErbB1 tyrosine phosphorylation and internalization. Basal ErbB tyrosine phosphorylation and ERK phosphorylation were inhibited by two different ErbB receptor tyrosine kinase inhibitors, by the ErbB1-specific neutralizing monoclonal antibody 225 IgG, by two different metalloproteinase inhibitors, and by neutralizing antibodies against amphiregulin (AR). In contrast, these responses were unaffected by neutralizing antibodies against other ErbB1 ligands or the ErbB2 inhibitors geldanamycin and AG825. The time course of autocrine ERK phosphorylation correlated with the appearance of soluble AR, and two different metalloproteinase inhibitors blocked AR release. These results define an amphiregulin- and ErbB1-dependent mechanism by which autocrine ERK activation is maintained in NHKs, even when ErbB1 autophosphorylation and internalization are limited.
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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.