Defective ubiquitinylation of EGFR mutants of lung cancer confers prolonged signaling.

Defective ubiquitinylation of EGFR mutants of lung cancer confers prolonged signaling. Research Abstract Details 

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Defective ubiquitinylation of EGFR mutants of lung cancer confers prolonged signaling. Abstract Text:

K Shtiegman,B S Kochupurakkal,Y Zwang,G Pines,A Starr,A Vexler,A Citri,M Katz,S Lavi,Y Ben-Basat,S Benjamin,S Corso,J Gan,R B Yosef,S Giordano,Y Yarden,

Several distinct mutations within the kinase domain of the epidermal growth factor receptor (EGFR) are associated with non-small cell lung cancer, but mechanisms underlying their oncogenic potential are incompletely understood. Although normally ligand-induced kinase activation targets EGFR to Cbl-mediated receptor ubiquitinylation and subsequent degradation in lysosomes, we report that certain EGFR mutants escape this regulation. Defective endocytosis characterizes a deletion mutant of EGFR, as well as a point mutant (L858R-EGFR), whose association with c-Cbl and ubiquitinylation are impaired. Our data raise the possibility that refractoriness of L858R-EGFR to downregulation is due to enhanced heterodimerization with the oncogene product HER2, which leads to persistent stimulation.

Defective ubiquitinylation of EGFR mutants of lung cancer confers prolonged signaling. Publishing Authors By Initials

K Shtiegman,BS Kochupurakkal,Y Zwang,G Pines,A Starr,A Vexler,A Citri,M Katz,S Lavi,Y Ben-Basat,S Benjamin,S Corso,J Gan,RB Yosef,S Giordano,Y Yarden,

For similar biochemical phenomena, metabolism, and nutrition: metabolism: ubiquitination research abstracts see: biochemical phenomena, metabolism, and nutrition: metabolism: ubiquitination research

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Defective ubiquitinylation of EGFR mutants of lung cancer confers prolonged signaling. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Oncogene

VOLUME: 26

Page Numbers: 6968-78

Journal Abbreviation: Oncogene

ISSN: 0950-9232

DAY: 7

MONTH: 05

YEAR: 2007

Defective ubiquitinylation of EGFR mutants of lung cancer confers prolonged signaling. Information

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LANGUAGE: eng

NlmUniqueID: 8711562

Defective ubiquitinylation of EGFR mutants of lung cancer confers prolonged signaling. Keywords Mesh Terms:

KEYWORDS: Ubiquitination

MESH TERMS: metabolism

Chemical & Substance for Abstract: Defective ubiquitinylation of EGFR mutants of lung cancer confers prolonged signaling. Information

Substance Name: Proto-Oncogene Proteins c-cbl

Registry Number: EC 6.3.2.-

Grant and Affiliation Information for Defective ubiquitinylation of EGFR mutants of lung cancer confers prolonged signaling.

AFFILIATION: Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel.

Country: England

AGENCY: United States NCI

GRANT: CA72981

ACRONYM: CA

MEDLINETA: Oncogene

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