Cavin-3 dictates the balance between ERK and Akt signaling.
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.
Department of Cell Biology , University of Texas Southwestern Medical Center , Dallas , United States.
Victor J
VJ
Hernandez
Jian
J
Weng
Peter
P
Ly
Shanica
S
Pompey
Hongyun
H
Dong
Lopa
L
Mishra
Margaret
M
Schwarz
Richard G W
RG
Anderson
Peter
P
Michaely
D017209:Apoptosis; D002460:Cell Line; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
C505360:CAVIN3 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases
Akt; Cavin-3; ERK; Human; Mouse; PRKCDBP; aerobic glycolysis; hSRBC