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PMID: 24069528 Published · epublish English Journal Article Research Support, N.I.H., Extramural

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

eLife ·Vol. 2 ·2013-09-24 ·Pages e00905

Hernandez VJ, Weng J, Ly P, Pompey S, Dong H, Mishra L, Schwarz M, Anderson RG, Michaely P

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
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
Chemicals
CAVIN3 protein, human Intracellular Signaling Peptides and Proteins Proto-Oncogene Proteins c-akt Extracellular Signal-Regulated MAP Kinases
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Hernandez Victor J
Department of Cell Biology , University of Texas Southwestern Medical Center , Dallas , United States.
Weng Jian
Ly Peter
Pompey Shanica
Dong Hongyun
Mishra Lopa
Schwarz Margaret
Anderson Richard G W
Michaely Peter
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Article Info
Journal
eLife
Abbr.
Elife
ISSN
2050-084X
DOI
10.7554/eLife.00905
Published
2013-09-24
Epub
2013-00-24
Pages
e00905
Language
English
Region
England
NLM ID
101579614
PMCID
PMC3780650
Subset
IM
Grants
NCI NIH HHS · P30 CA016672 · United States
NCI NIH HHS · P01 CA130821 · United States
NCI NIH HHS · CA130821 · United States
NIGMS NIH HHS · GM052016 · United States
NHLBI NIH HHS · R01 HL085218 · United States
NHLBI NIH HHS · HL085218 · United States
NHLBI NIH HHS · R01 HL114977 · United States
NCRR NIH HHS · C06 RR030414 · United States
NIGMS NIH HHS · R01 GM052016 · United States
Corrections
CommentIn
PMID: 24069530
External Links
PubMed source DOI: 10.7554/eLife.00905 PMC Full Text View journal details
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