File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Phosphorylation of TNF-α converting enzyme by gastrin-releasing peptide induces amphiregulin release and EGF receptor activation

TitlePhosphorylation of TNF-α converting enzyme by gastrin-releasing peptide induces amphiregulin release and EGF receptor activation
Authors
Issue Date2006
Citation
Proceedings of the National Academy of Sciences of the United States of America, 2006, v. 103 n. 18, p. 6901-6906 How to Cite?
AbstractG protein-coupled receptors induce EGF receptor (EGFR) signaling, leading to the proliferation and invasion of cancer cells. Elucidation of the mechanism of EGFR activation by G protein-coupled receptors may identify new signaling paradigms. A gastrin-releasing peptide (GRP)/GRP receptor-mediated autocrine pathway was previously described in squamous cell carcinoma of head and neck. In the present study, we demonstrate that TNF-α converting enzyme (TACE), a disintegrin and metalloproteinse-17, undergoes a Src-dependent phosphorylation that regulates release of the EGFR ligand amphiregulin upon GRP treatment. Further investigation reveals the phosphatidylinositol 3-kinase (PI3-K) as the intermediate of c-Src and TACE, contributing to their association and TACE phosphorylation, phosphoinositide-dependent kinase 1 (PDK1), a downstream target of PI3-K, has been identified as the previously undescribed kinase to directly phosphorylate TACE upon GRP treatment. These findings suggest a signaling cascade of GRP-Src-PI3-K-PDK1-TACE-amphiregulin-EGFR with multiple points of interaction, translocation, and phosphorylation. Furthermore, knockdown of PDK1 augmented the antitumor effects of the EGFR inhibitor erlotinib, indicating PDK1 as a therapeutic target to improve the clinical response to EGFR inhibitors. © 2006 by The National Academy of Sciences of the USA.
Persistent Identifierhttp://hdl.handle.net/10722/194160
ISSN
2015 Impact Factor: 9.423
2015 SCImago Journal Rankings: 6.883
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZhang, Q-
dc.contributor.authorThomas, SM-
dc.contributor.authorLui, VWY-
dc.contributor.authorXi, S-
dc.contributor.authorSiegfried, JM-
dc.contributor.authorFan, H-
dc.contributor.authorSmithgall, TE-
dc.contributor.authorMills, GB-
dc.contributor.authorGrandis, JR-
dc.date.accessioned2014-01-30T03:32:14Z-
dc.date.available2014-01-30T03:32:14Z-
dc.date.issued2006-
dc.identifier.citationProceedings of the National Academy of Sciences of the United States of America, 2006, v. 103 n. 18, p. 6901-6906-
dc.identifier.issn0027-8424-
dc.identifier.urihttp://hdl.handle.net/10722/194160-
dc.description.abstractG protein-coupled receptors induce EGF receptor (EGFR) signaling, leading to the proliferation and invasion of cancer cells. Elucidation of the mechanism of EGFR activation by G protein-coupled receptors may identify new signaling paradigms. A gastrin-releasing peptide (GRP)/GRP receptor-mediated autocrine pathway was previously described in squamous cell carcinoma of head and neck. In the present study, we demonstrate that TNF-α converting enzyme (TACE), a disintegrin and metalloproteinse-17, undergoes a Src-dependent phosphorylation that regulates release of the EGFR ligand amphiregulin upon GRP treatment. Further investigation reveals the phosphatidylinositol 3-kinase (PI3-K) as the intermediate of c-Src and TACE, contributing to their association and TACE phosphorylation, phosphoinositide-dependent kinase 1 (PDK1), a downstream target of PI3-K, has been identified as the previously undescribed kinase to directly phosphorylate TACE upon GRP treatment. These findings suggest a signaling cascade of GRP-Src-PI3-K-PDK1-TACE-amphiregulin-EGFR with multiple points of interaction, translocation, and phosphorylation. Furthermore, knockdown of PDK1 augmented the antitumor effects of the EGFR inhibitor erlotinib, indicating PDK1 as a therapeutic target to improve the clinical response to EGFR inhibitors. © 2006 by The National Academy of Sciences of the USA.-
dc.languageeng-
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of America-
dc.titlePhosphorylation of TNF-α converting enzyme by gastrin-releasing peptide induces amphiregulin release and EGF receptor activation-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1073/pnas.0509719103-
dc.identifier.pmid16641105-
dc.identifier.scopuseid_2-s2.0-33646468634-
dc.identifier.volume103-
dc.identifier.issue18-
dc.identifier.spage6901-
dc.identifier.epage6906-
dc.identifier.isiWOS:000237399900023-
dc.identifier.f10001033446-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats