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Epidermal growth factor receptor induced apoptosis: potentiation by inhibition of Ras signaling
Author(s) -
Högnason Thorbergur,
Chatterjee Sukalyan,
Vartanian Timothy,
Ratan Rajiv R,
Ernewein Krista M,
Habib Amyn A
Publication year - 2001
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(01)02166-4
Subject(s) - autophosphorylation , epidermal growth factor receptor , apoptosis , microbiology and biotechnology , growth factor receptor , cancer research , egfr inhibitors , biology , long term potentiation , signal transduction , insulin like growth factor 1 receptor , epidermal growth factor , receptor tyrosine kinase , tyrosine kinase , kinase , growth factor , receptor , protein kinase a , biochemistry
Previous studies have shown that certain tumor cell lines which naturally express high levels of the epidermal growth factor receptor (EGFR) undergo apoptosis when exposed to epidermal growth factor. Whether this phenomenon is a direct result of receptor overexpression or some other genetic alteration renders these cells sensitive to apoptosis is yet to be established. We show that experimentally increasing the level of EGFR expression predictably leads to apoptosis in a variety of cell types which requires an active tyrosine kinase but not EGFR autophosphorylation sites. Expression of a dominant negative Ras mutant in EGFR overexpressing cells results in a significant potentiation of EGFR induced apoptosis suggesting that Ras activation is a key survival signal generated by the EGFR. We propose that potentiation of EGFR induced apoptosis by dominant negative Ras results, at least in part, by a block of Akt activation.