title: The Catalytic Efficiency of Lipin 1β Increases by Physically Interacting with the Proto-oncoprotein c-Fos.
abstract: Phosphatidic acid (PA) is a central precursor for membrane phospholipid biosynthesis. The lipin family is a magnesium-dependent type I PA phosphatase involved in de novo synthesis of neutral lipids and phospholipids. The regulation of lipin activity may govern the pathways by which these lipids are synthesized and control the cellular levels of important signaling lipids. Moreover, the proto-oncoprotein c-Fos has an emerging role in glycerolipid synthesis regulation; by interacting with key synthesizing enzymes it is able to increase overall phospho- and glycolipid synthesis. We studied the lipin 1β enzyme activity in a cell-free system using PA/Triton X-100 mixed micelles as substrate, analyzing it in the presence/absence of c-Fos. We found that lipin 1β kcat value increases around 40% in the presence of c-Fos, with no change in the lipin 1β affinity for the PA/Triton X-100 mixed micelles. We also probed a physical interaction between both proteins. Although the c-Fos domain involved in lipin activation is its basic domain, the interaction domain is mapped to the N-terminal c-Fos. In conclusion, we provide evidence for a novel positive regulator of lipin 1β PA phosphatase activity that is not achieved via altering its subcellular localization or affinity for membranes but rather through directly increasing its catalytic efficiency.
authors.affiliation: From the Centro de Investigaciones en Química Biológica de Córdoba (Consejo Nacional de Investigaciones Científicas y Técnicas), Departamento de Química Biológica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, X5000HUA Córdoba and.
authors.forename: Andres M
authors.identifier: http://orcid.org/0000-0003-3894-1845
authors.initials: AM
authors.lastname: Cardozo Gizzi
authors.affiliation: From the Centro de Investigaciones en Química Biológica de Córdoba (Consejo Nacional de Investigaciones Científicas y Técnicas), Departamento de Química Biológica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, X5000HUA Córdoba and.
authors.forename: Cesar G
authors.initials: CG
authors.lastname: Prucca
authors.affiliation: the Instituto de Investigaciones Bioquímicas de Bahía Blanca, Universidad Nacional del Sur-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Edificio El Camino La Carrindanga Km 7, 8000 Bahía Blanca, Argentina.
authors.forename: Virginia L
authors.initials: VL
authors.lastname: Gaveglio
authors.affiliation: From the Centro de Investigaciones en Química Biológica de Córdoba (Consejo Nacional de Investigaciones Científicas y Técnicas), Departamento de Química Biológica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, X5000HUA Córdoba and.
authors.forename: Marianne L
authors.initials: ML
authors.lastname: Renner
authors.affiliation: the Instituto de Investigaciones Bioquímicas de Bahía Blanca, Universidad Nacional del Sur-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Edificio El Camino La Carrindanga Km 7, 8000 Bahía Blanca, Argentina.
authors.forename: Susana J
authors.initials: SJ
authors.lastname: Pasquaré
authors.affiliation: From the Centro de Investigaciones en Química Biológica de Córdoba (Consejo Nacional de Investigaciones Científicas y Técnicas), Departamento de Química Biológica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, X5000HUA Córdoba and bcaputto@fcq.unc.edu.ar.
authors.forename: Beatriz L
authors.initials: BL
authors.lastname: Caputto
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004075:Diglycerides / Q000737:chemistry; D031541:Fluorescence Resonance Energy Transfer; D017353:Gene Deletion; D006801:Humans; D008055:Lipids / Q000737:chemistry; D051379:Mice; D008823:Micelles; D009687:Nuclear Proteins / Q000378:metabolism*; D009930:Organic Chemicals / Q000737:chemistry; D010711:Phosphatidate Phosphatase / Q000378:metabolism*; D010712:Phosphatidic Acids / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry; D017354:Point Mutation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D004075:Diglycerides; D008055:Lipids; D008823:Micelles; D009687:Nuclear Proteins; D009930:Organic Chemicals; D010712:Phosphatidic Acids; D010743:Phospholipids; D016760:Proto-Oncogene Proteins c-fos; D011994:Recombinant Proteins; C088310:lipine; C485999:LPIN1 protein, human; C418978:Lpin1 protein, mouse; D010711:Phosphatidate Phosphatase
keywords: Forster resonance energy transfer; c-Fos; enzyme mechanism; lipin; membrane biogenesis; phosphatase; phosphatidic acid; phospholipid metabolism; protein/protein interaction