Cavin-3 Dictates the Balance Between ERK and Akt Signaling

Overview

Journal Elife

Specialty Biology

Date 2013 Sep 27

PMID 24069528

Citations 37

Authors

Victor J Hernandez

Jian Weng

Peter Ly

Shanica Pompey

Hongyun Dong

Lopa Mishra

Margaret Schwarz

Richard G W Anderson

Peter Michaely

Affiliations

Soon will be listed here.

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.

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