FGF-2 protects small cell lung cancer cells from apoptosis through a complex involving PKCɛ, B-Raf and S6K2
Open Access
- 29 June 2006
- journal article
- research article
- Published by Springer Nature in The EMBO Journal
- Vol. 25 (13) , 3078-3088
- https://doi.org/10.1038/sj.emboj.7601198
Abstract
Patients with small cell lung cancer (SCLC) die because of chemoresistance. Fibroblast growth factor‐2 (FGF‐2) increases the expression of antiapoptotic proteins, XIAP and Bcl‐XL, and triggers chemoresistance in SCLC cells. Here we show that these effects are mediated through the formation of a specific multiprotein complex comprising B‐Raf, PKCε and S6K2. S6K1, Raf‐1 and other PKC isoforms do not form similar complexes. RNAi‐mediated downregulation of B‐Raf, PKCε or S6K2 abolishes FGF‐2‐mediated survival. In contrast, overexpression of PKCε increases XIAP and Bcl‐XL levels and chemoresistance in SCLC cells. In a tetracycline‐inducible system, increased S6K2 kinase activity triggers upregulation of XIAP, Bcl‐XL and prosurvival effects. However, increased S6K1 kinase activity has no such effect. Thus, S6K2 but not S6K1 mediates prosurvival/chemoresistance signalling.Keywords
This publication has 38 references indexed in Scilit:
- B-Raf Inhibits Programmed Cell Death Downstream of Cytochrome c Release from Mitochondria by Activating the MEK/Erk PathwayMolecular and Cellular Biology, 1999
- Novel Roles of Specific Isoforms of Protein Kinase C in Activation of the c-fos Serum Response ElementMolecular and Cellular Biology, 1999
- Disruption of the p70s6k/p85s6k gene reveals a small mouse phenotype and a new functional S6 kinaseThe EMBO Journal, 1998
- Molecular Cloning and Characterization of a Novel p70 S6 Kinase, p70 S6 Kinase β Containing a Proline-rich RegionJournal of Biological Chemistry, 1998
- Peptide modulators of protein–protein interactions in intracellular signalingNature Biotechnology, 1998
- Activation of the Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Pathway by Conventional, Novel, and Atypical Protein Kinase C IsotypesMolecular and Cellular Biology, 1998
- A Truncated HIV-1 Tat Protein Basic Domain Rapidly Translocates through the Plasma Membrane and Accumulates in the Cell NucleusJournal of Biological Chemistry, 1997
- Translocation Inhibitors Define Specificity of Protein Kinase C Isoenzymes in Pancreatic β-CellsPublished by Elsevier ,1997
- Protein Kinase C, but Not Tyrosine Kinases or Ras, Plays a Critical Role in Angiotensin II-induced Activation of Raf-1 Kinase and Extracellular Signal-regulated Protein Kinases in Cardiac MyocytesJournal of Biological Chemistry, 1996
- Regulation of BCR- and PKCCa2+-mediated activation of the Raf1/MEK/MAPK pathway by protein-tyrosine kinase and -tyrosine phosphatase activitiesMolecular Immunology, 1996