Cavin-3 dictates the balance between ERK and Akt signaling

Victor J. Hernandez, Jian Weng, Peter Ly, Shanica Pompey, Hongyun Dong, Lopa Mishra, Margaret Schwarz, Richard G.W. Anderson, Peter Michaely

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31 Scopus citations

Abstract

Cavin-3 is a tumor suppressor protein of unknown function. Using both in vivo and in vitro approaches, we show that cavin-3 dictates the balance between ERK and Akt signaling. Loss of cavin-3 increases Akt signaling at the expense of ERK, while gain of cavin-3 increases ERK signaling at the expense Akt. Cavin-3 facilitates signal transduction to ERK by anchoring caveolae to the membrane skeleton of the plasma membrane via myosin-1c. Caveolae are lipid raft specializations that contain an ERK activation module and loss of the cavin-3 linkage reduces the abundance of caveolae, thereby separating this ERK activation module from signaling receptors. Loss of cavin-3 promotes Akt signaling through suppression of EGR1 and PTEN. The in vitro consequences of the loss of cavin-3 include induction of Warburg metabolism (aerobic glycolysis), accelerated cell proliferation, and resistance to apoptosis. The in vivo consequences of cavin-3 knockout are increased lactate production and cachexia.

Original languageEnglish (US)
Article numbere00905
JournaleLife
Volume2013
Issue number2
DOIs
StatePublished - Sep 24 2013

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ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Hernandez, V. J., Weng, J., Ly, P., Pompey, S., Dong, H., Mishra, L., Schwarz, M., Anderson, R. G. W., & Michaely, P. (2013). Cavin-3 dictates the balance between ERK and Akt signaling. eLife, 2013(2), [e00905]. https://doi.org/10.7554/eLife.00905