Epidermal growth factor protects prostate cancer cells from apoptosis by inducing BAD phosphorylation via redundant signaling pathways

Seetharama S. Konduru, Yelena Karpova, George Kulik

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Protection from apoptosis by receptor tyrosine kinases, resistant to the inhibition of phosphatidylinositol 3′-kinase/Akt and Ras/MEK pathways, has been reported in several cell types, including fibroblasts and epithelial prostate cancer cells; however, mechanisms of this effect were not clear. Here we report that in prostate cancer cells, epidermal growth factor activates two antiapoptotic signaling pathways that impinge on the proapoptotic protein BAD. One signaling cascade operates via the Ras/MEK module and induces BAD phosphorylation on Ser112. Another pathway predominantly relies on Rac/PAK1 signaling that leads to BAD phosphorylation on Ser136. Each of these two pathways is sufficient to protect cells from apoptosis, and therefore both have to be inhibited simultaneously to block epidermal growth factor-dependent survival. Redundancy of antiapoptotic signaling pathways should be considered when therapies targeting antiapoptotic mechanisms are designed.

Original languageEnglish
Pages (from-to)27367-27377
Number of pages11
JournalJournal of Biological Chemistry
Volume281
Issue number37
DOIs
Publication statusPublished - 15 Sep 2006
Externally publishedYes

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Phosphorylation
Epidermal Growth Factor
Prostatic Neoplasms
Cells
Apoptosis
Mitogen-Activated Protein Kinase Kinases
Phosphatidylinositol 3-Kinase
Receptor Protein-Tyrosine Kinases
Fibroblasts
Redundancy
Proteins
Therapeutics

ASJC Scopus subject areas

  • Biochemistry

Cite this

Epidermal growth factor protects prostate cancer cells from apoptosis by inducing BAD phosphorylation via redundant signaling pathways. / Konduru, Seetharama S.; Karpova, Yelena; Kulik, George.

In: Journal of Biological Chemistry, Vol. 281, No. 37, 15.09.2006, p. 27367-27377.

Research output: Contribution to journalArticle

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