Format

Send to

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

Cavin-3 dictates the balance between ERK and Akt signaling.

Author information

1
Department of Cell Biology , University of Texas Southwestern Medical Center , Dallas , United States.

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

PMID:
24069528
PMCID:
PMC3780650
DOI:
10.7554/eLife.00905
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for eLife Sciences Publications, Ltd Icon for PubMed Central
Loading ...
Support Center