+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Amphiregulin induces tyrosine phosphorylation of the epidermal growth factor receptor and p185erbB2. Evidence that amphiregulin acts exclusively through the epidermal growth factor receptor at the surface of human epithelial cells



Amphiregulin induces tyrosine phosphorylation of the epidermal growth factor receptor and p185erbB2. Evidence that amphiregulin acts exclusively through the epidermal growth factor receptor at the surface of human epithelial cells



Journal of Biological Chemistry 268(4): 2924-2931



The COOH-terminal half of the amphiregulin (AR) molecule has sequence homology to epidermal growth factor (EGF). The ability of AR to elicit in vivo phosphorylation of the EGF receptor (EGFR) and p185-erbB2 was studied in four human epithelial cell lines which expressed either or both of the receptor tyrosine kinases. AR induced the phosphorylation of the EGFR and p185-erbB2, and phosphoamino acid analysis revealed enhanced phosphorylation of tyrosine residues in both receptor proteins. A monoclonal antibody (mAb) which binds to the extracellular domain of the EGFR blocked the phosphorylation of the EGFR and p185-erbB2 as well as AR-induced mitogenesis indicating that the EGFR mediated these responses. In MDA-MB-453 cells which lack EGFRs, AR did not induce phosphorylation of p185-erbB2, did not affect proliferation, and had no detectable effect on the phosphorylation of cellular proteins isolated using an anti-phosphotyrosine mAb. Qualitatively, in vivo phosphorylations induced by AR and EGF were found to be indistinguishable as demonstrated by analysis of cellular 32P-labeled proteins isolated with the anti-phosphotyrosine mAb. Moreover, in the presence of the anti-EGFR mAb, AR had no effect on the proliferation of cells. These results provide strong evidence that the EGFR is the sole cell surface mediator of the action of AR in human epithelial cells.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 008136960

Download citation: RISBibTeXText

PMID: 7679104


Related references

STAT activation by epidermal growth factor (EGF) and amphiregulin. Requirement for the EGF receptor kinase but not for tyrosine phosphorylation sites or JAK1. Journal of Biological Chemistry 271(16): 9185-9188, 1996

Amphiregulin triggered epidermal growth factor receptor activation confers in vivo crizotinib-resistance of EML4-ALK lung cancer and circumvention by epidermal growth factor receptor inhibitors. Cancer Science 108(1): 53-60, 2017

Epidermal growth factor receptor pathway analysis identifies amphiregulin as a key factor for cisplatin resistance of human breast cancer cells. Journal of Biological Chemistry 283(2): 739-750, 2008

Sa1865 Helicobacter pylori Induces Phosphorylation of Epidermal Growth Factor Receptor via p38/Erk Activation in Gastric Epithelial Cells in Heparin Binding-Epidermal Growth Factor Independent Manner. Gastroenterology 144(5): S-323, 2013

Expression of amphiregulin and epidermal growth factor receptor in human breast cancer: Analysis of autocriny and stromal-epithelial interactions. Journal of Pathology 194(4): 413-419, 2001

The epidermal growth factor receptor couples transforming growth factor-alpha, heparin-binding epidermal growth factor-like factor, and amphiregulin to Neu, ErbB-3, and ErbB-4. Journal of Biological Chemistry 271(33): 20047-20052, 1996

Quantitation of the mRNA expression of the epidermal growth factor system: selective induction of heparin-binding epidermal growth factor-like growth factor and amphiregulin expression by growth factor stimulation of prostate stromal cells. Journal of Laboratory and Clinical Medicine 136(3): 209-217, 2000

The epidermal growth factor receptor couples transforming growth factor-a, heparin-binding epidermal growth factor-like factor, and amphiregulin to Neu, ErbB-3, and ErbB-4. The Journal of Biological Chemistry 271: 047-52, 1996

Amphiregulin, epidermal growth factor receptor, and estrogen receptor expression in human primary breast cancer. Cancer Research 53(15): 3597-3602, 1993

Impact of epidermal growth factor receptor gene expression level on clinical outcomes in epidermal growth factor receptor mutant lung adenocarcinoma patients taking first-line epidermal growth factor receptor-tyrosine kinase inhibitors. Tumour Biology 39(3): 1010428317695939, 2017

Retinoid-induced epidermal hyperplasia is mediated by epidermal growth factor receptor activation via specific induction of its ligands heparin binding-EGF and amphiregulin in human skin in vivo. Journal of Investigative Dermatology 122(3): A49, 2004

Retinoid-induced epidermal hyperplasia is mediated by epidermal growth factor receptor activation via specific induction of its ligands heparin-binding EGF and amphiregulin in human skin in vivo. Journal of Investigative Dermatology 126(4): 732-739, 2006

Epidermal growth factor receptor-dependent stimulation of amphiregulin expression in androgen-stimulated human prostate cancer cells. Molecular Biology of the Cell 5(3): 339-347, 1994

A new model system identifies epidermal growth factor receptor-human epidermal growth factor receptor 2 (HER2) and HER2-human epidermal growth factor receptor 3 heterodimers as potent inducers of oesophageal epithelial cell invasion. Journal of Pathology 243(4): 481-495, 2017

Macrophage-Inflammatory Protein-3a Mediates Epidermal Growth Factor Receptor Transactivation and ERK1/2 MAPK Signaling in Caco-2 Colonic Epithelial Cells via Metalloproteinase-Dependent Release of Amphiregulin. Journal of Immunology 178(12): 13-21, 2007