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JNK and ceramide kinase govern the biogenesis of lipid droplets through activation of group IVA phospholipase A2
Gubern Burset, Albert (Universitat Autònoma de Barcelona. Institut de Neurociències)
Barceló Torns, Miquel (Universitat Autònoma de Barcelona. Institut de Neurociències)
Barneda, David (Universitat Autònoma de Barcelona. Institut de Neurociències)
López, José M. (Universitat Autònoma de Barcelona. Institut de Neurociències)
Masgrau Juanola, Roser (Universitat Autònoma de Barcelona. Departament de Bioquímica i Biologia Molecular)
Picatoste Ramón, Fernando (Universitat Autònoma de Barcelona. Institut de Neurociències)
Chalfant, Charles E. (Virginia Commonwealth University. School of Medicine)
Balsinde, Jesús (Consejo Superior de Investigaciones Científicas. Instituto de Biología y Genética Molecular)
Balboa María A. (Consejo Superior de Investigaciones Científicas. Instituto de Biología y Genética Molecular)
Claro Izaguirre, Enrique (Universitat Autònoma de Barcelona. Departament de Bioquímica i Biologia Molecular)

Date: 2009
Abstract: The biogenesis of lipid droplets (LD) induced by serum depends on group IVA phospholipase A2 (cPLA2α). This work dissects the pathway leading to cPLA2α activation and LD biogenesis. Both processes were Ca2+-independent, as they took place after pharmacological blockade of Ca2+ transients elicited by serum or chelation with 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid tetrakis(acetoxymethyl ester). The single mutation D43N in cPLA2α, which abrogates its Ca2+ binding capacity and translocation to membranes, did not affect enzyme activation and formation of LD. In contrast, the mutation S505A did not affect membrane relocation of the enzyme in response to Ca2+ but prevented its phosphorylation, activation, and the appearance of LD. Expression of specific activators of different mitogen-activated protein kinases showed that phosphorylation of cPLA2α at Ser-505 is due to JNK. This was confirmed by pharmacological inhibition and expression of a dominant-negative form of the upstream activator MEKK1. LD biogenesis was accompanied by increased synthesis of ceramide 1-phosphate. Overexpression of its synthesizing enzyme ceramide kinase increased phosphorylation of cPLA2α at Ser-505 and formation of LD, and its down-regulation blocked the phosphorylation of cPLA2α and LD biogenesis. These results demonstrate that LD biogenesis induced by serum is regulated by JNK and ceramide kinase.
Note: Número d'acord de subvenció NIH/HL-072925
Note: Número d'acord de subvenció NIH/CA-117990
Note: Número d'acord de subvenció MEC/SAF 2004-01698
Note: Número d'acord de subvenció MEC/SAF 2007-60055
Note: Número d'acord de subvenció MEC/BFU 2009-07823
Note: Número d'acord de subvenció MSPS/PI05/1723
Rights: Tots els drets reservats.
Language: Anglès.
Document: article ; recerca ; publishedVersion
Subject: Acetoxymethyl esters ; Binding capacities ; Ceramide 1-phosphate ; Ceramides ; Down-regulation ; Enzyme activation ; Lipid droplets ; Mitogen activated protein kinase ; Over-expression ; Pharmacological blockade ; Pharmacological inhibition ; Phospholipase A ; Single mutation ; Tetraacetic acid ; Tetrakis
Published in: The Journal of biological chemistry, Vol. 284, Num. 47 (2009) , p. 32359-32369, ISSN 0021-9258

DOI: 10.1074/jbc.M109.061515
PMID: 19778898


11 p, 2.3 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (scientific output) > Health sciences and biosciences > Institut de Neurociències (INc)
Articles > Research articles
Articles > Published articles

 Record created 2015-01-29, last modified 2019-05-23



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