Cavin-3 dictates the balance between ERK and Akt signaling

Elife. 2013 Sep 24;2:e00905. doi: 10.7554/eLife.00905.

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. DOI:http://dx.doi.org/10.7554/eLife.00905.001.

Keywords: Akt; Cavin-3; ERK; Human; Mouse; PRKCDBP; aerobic glycolysis; hSRBC.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Apoptosis
  • Cell Line
  • Enzyme Activation
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Humans
  • Intracellular Signaling Peptides and Proteins / physiology*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / physiology*

Substances

  • CAVIN3 protein, human
  • Intracellular Signaling Peptides and Proteins
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases