José Luís Rosa

Institut d'Investigació Biomédica de Bellvitge

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Francesc Ventura

Institut d'Investigació Biomédica de Bellvitge

Ramón Bartrons

Weatherford College

Monica Cubillos‐Rojas

Institute for Research in Biomedicine

Jarbas Rodrigues de Oliveira

Pontifícia Universidade Católica do Rio Grande do Sul

Leonardo Pedrazza

Institut d'Investigació Biomédica de Bellvitge

José Antonio Valer

Institut d'Investigació Biomédica de Bellvitge

Santiago Ambrosio

Universitat de Barcelona

Taiane Schneider

Universitat de Barcelona

Carolina Pimenta-Lopes

Institut d'Investigació Biomédica de Bellvitge

Eddie Rodríguez-Carballo

University of Geneva

Cooperative Institutions

Inserm

239

Centre National de la Recherche Scientifique

190

University of Michigan–Ann Arbor

173

Harvard University

161

Universitat de Barcelona

161

National Institutes of Health

116

Chinese Academy of Sciences

111

Washtenaw Community College

105

Université Paris Cité

UiT The Arctic University of Norway

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Direct Binding of Smad1 and Smad4 to Two Distinct Motifs Mediates Bone Morphogenetic Protein-specific Transcriptional Activation ofId1 Gene

Journal of Biological Chemistry (2002)

Teresa López‐Rovira Elisabet Chalaux Joan Massagué José Luís Rosa Francesc Ventura

Bone morphogenetic proteins (BMPs) are potent inhibitors of myoblast differentiation and inducers of bone formation both in vivo and in vitro. Expression of Id1, a negative regulator of basic helix-loop-helix transcription factors, is up-regulated by BMPs and contributes to the antimyogenic effects of this family of cytokines. In this report, we have identified a specific BMP-2 immediate early response enhancer in the human Id1gene. Transcriptional activation of the enhancer was increased by overexpression of BMP-responsive Smads, and Smad4 and was completely abrogated in Smad4-deficient cells. Deletion analysis demonstrates that the responsive region is composed of two separate DNA binding elements, a set of overlapping GC boxes, which bind BMP-regulated Smads upon BMP stimulation, and three repeats of CAGAC boxes. Gel shift and oligonucleotide pull-down assays demonstrated that these two types of motifs were capable of binding their corresponding Smads. However, deletion or mutation of either DNA binding element was nonadditive, since disruption of either GC or CAGAC boxes resulted in complete or severe loss of BMP-2 responsiveness. These data suggest the simultaneous requirement of two independent DNA binding elements to allow functional cooperativity of BMP-regulated Smads and Smad4 in BMP-activated gene promoters.

Cooperativity

Transcription

10.1074/jbc.m106826200

Cite

Citations (279)

Abnormal α-Synuclein Interactions with Rab Proteins in α-Synuclein A30P Transgenic Mice

Journal of Neuropathology & Experimental Neurology (2004)

Esther Dalfó Teresa Gómez‐Isla José Luís Rosa María Nieto Bodelón Mar Cuadrado‐Tejedor

Mutation A30P in the alpha-synuclein gene is a cause of familial Parkinson disease. Transgenic mice expressing wild mouse and mutant human A30P alpha-synuclein, Tg5093 mice (Tg), show a progressive motor disorder characterized by tremor, rigidity, and dystonia, accompanied by accumulation of alpha-synuclein in the soma and neurites and by a conspicuous gliosis beginning in the hippocampal formation at the age of 7 to 8 months and spreading throughout the CNS. Impaired short-term changes in synaptic strength have also been documented in hippocampal slices from Tg mice. Alpha-synuclein aggregates of approximately 34 and 70 kDa, in addition to the band of 17 kDa, corresponding to the molecular weight of alpha-synuclein, were recovered in the PBS-soluble fraction of brain homogenates from Tg mice but not from brain samples from age-matched wildtype littermates. MPTP-treated Tg and wildtype mice produced alpha-synuclein aggregates in the PBS-, deoxycholate-, and SDS-soluble fractions. Aggregates of alpha-synuclein, although with different molecular weights, were also observed in rotenone-treated Tg and wildtype mice. Pull-down studies with members of the Rab protein family have shown that alpha-synuclein from Tg mice interacts with Rab3a, Rab5, and Rab8. This binding is not due to the amount of alpha-synuclein (levels of which are higher in Tg mice) and it is not dependent on the amount of Rab protein used in the assay. Rather, alpha-synuclein interactions with Rab proteins are due to mutant alpha-synuclein as demonstrated in Rab pull-down assays with recombinant of wildtype and mutant A30P human alpha-synuclein. Since Rab3a, Rab5, and Rab8 are important proteins involved in synaptic vesicle trafficking and exocytosis at the synapse, vesicle endocytosis, and trans-Golgi transport, respectively, it can be suggested that these functions are impaired in Tg mice. This rationale is consistent with previous data showing that short-term hippocampal synaptic plasticity is altered and that alpha-synuclein accumulates in the cytoplasm of neurons in Tg mice.

Rab

Wild type

Gliosis

Gene knockin

10.1093/jnen/63.4.302

Cite

Citations (102)

Contribution of S6K1/MAPK Signaling Pathways in the Response to Oxidative Stress: Activation of RSK and MSK by Hydrogen Peroxide

PLoS ONE (2013)

Anna Maria Siebel Monica Cubillos‐Rojas Roberto Christ Vianna Santos Taiane Schneider Carla Denise Bonan

Cells respond to different kind of stress through the coordinated activation of signaling pathways such as MAPK or p53. To find which molecular mechanisms are involved, we need to understand their cell adaptation. The ribosomal protein, S6 kinase 1 (S6K1), is a common downstream target of signaling by hormonal or nutritional stress. Here, we investigated the initial contribution of S6K1/MAPK signaling pathways in the cell response to oxidative stress produced by hydrogen peroxide (H2O2). To analyze S6K1 activation, we used the commercial anti-phospho-Thr389-S6K1 antibody most frequently mentioned in the bibliography. We found that this antibody detected an 80-90 kDa protein that was rapidly phosphorylated in response to H2O2 in several human cells. Unexpectedly, this phosphorylation was insensitive to both mTOR and PI3K inhibitors, and knock-down experiments showed that this protein was not S6K1. RSK and MSK proteins were candidate targets of this phosphorylation. We demonstrated that H2O2 stimulated phosphorylation of RSK and MSK kinases at residues that are homologous to Thr389 in S6K1. This phosphorylation required the activity of either p38 or ERK MAP kinases. Kinase assays showed activation of RSK and MSK by H2O2. Experiments with mouse embryonic fibroblasts from p38 animals’ knockout confirmed these observations. Altogether, these findings show that the S6K1 signaling pathway is not activated under these conditions, clarify previous observations probably misinterpreted by non-specific detection of proteins RSK and MSK by the anti-phospho-Thr389-S6K1 antibody, and demonstrate the specific activation of MAPK signaling pathways through ERK/p38/RSK/MSK by H2O2.

Ribosomal s6 kinase

10.1371/journal.pone.0075523

Cite

Citations (18)

A nonsense variant in HERC1 is associated with intellectual disability, megalencephaly, thick corpus callosum and cerebellar atrophy

European Journal of Human Genetics (2015)

Lam Son Nguyen Taiane Schneider Marlène Rio Sébastien Moutton Karine Siquier-Pernet

Megalencephaly

Nonsense mutation

Proband

10.1038/ejhg.2015.140

Cite

Citations (46)

Tris-Acetate Polyacrylamide Gradient Gels for the Simultaneous Electrophoretic Analysis of Proteins of Very High and Low Molecular Mass

Methods in molecular biology (2018)

Monica Cubillos‐Rojas Fabiola Amair‐Pinedo Irantzu Tato Ramón Bartrons Francesc Ventura

Polyacrylamide

Coomassie Brilliant Blue

Molecular mass

10.1007/978-1-4939-8793-1_22

Cite

Citations (7)

Gene Expression of Glucokinase Regulatory Protein in Regenerating Rat Liver

Hepatology (1997)

José Luís Rosa J.X. Pérez Michel Detheux Emile Van Schaftingen Ramón Bartrons

The activity and messenger RNA (mRNA) levels of glucokinase, and the concentration and mRNA levels of its regulatory protein, were analyzed during liver regeneration. The activity of glucokinase and the concentration of its regulatory protein decreased to 30% and 50%, respectively, after liver resection, remaining low after 1 week. No significant variations in the level of these proteins were found in sham-operated animals. The regulatory protein/glucokinase molar ratio increased during the replicative phase, to a maximum at 48 hours. The mRNA levels of glucokinase and of its regulatory protein decreased rapidly after partial hepatectomy to minimum values at 6 hours (15%) and at 12 hours (4%), respectively, returning to normal values at 24 hours and 168 hours, respectively. Sham-operated animals showed a similar decrease in mRNA levels during the prereplicative phase of liver regeneration, suggesting that the initial effects observed in the gene expression of these proteins were due to surgical stress. During the replicative phase, a specific inhibition of the regulatory protein's gene expression was observed in the regenerating liver. A decrease in the content of regulatory protein and the glucokinase activity, and an increase in the molar ratio of these two proteins correlate with the observed decrease in glycolytic flux, providing further evidence that the phosphorylation of glucose is a control point in the glycolytic/gluconeogenic flux during liver regeneration.

Glucokinase

Liver Regeneration

Gluconeogenesis

10.1002/hep.510250212

Cite

Citations (7)

HERC1 Ubiquitin Ligase Is Required for Normal Axonal Myelination in the Peripheral Nervous System

Molecular Neurobiology (2018)

Sara Bachiller María Angustias Roca-Ceballos Irene García-Domínguez Eva M. Pérez-Villegas David Martos-Carmona

Peripheral Nervous System

Schwann cell

10.1007/s12035-018-1021-0

Cite

Citations (18)

The p38/MK2/Hsp25 Pathway Is Required for BMP-2-Induced Cell Migration

PLoS ONE (2011)

Cristina Gamell Antonio G. Susperregui Ora Bernard José Luís Rosa Francesc Ventura

Background Bone morphogenetic proteins (BMPs) have been shown to participate in the patterning and specification of several tissues and organs during development and to regulate cell growth, differentiation and migration in different cell types. BMP-mediated cell migration requires activation of the small GTPase Cdc42 and LIMK1 activities. In our earlier report we showed that activation of LIMK1 also requires the activation of PAKs through Cdc42 and PI3K. However, the requirement of additional signaling is not clearly known. Methodology/Principal Findings Activation of p38 MAPK has been shown to be relevant for a number of BMP-2′s physiological effects. We report here that BMP-2 regulation of cell migration and actin cytoskeleton remodelling are dependent on p38 activity. BMP-2 treatment of mesenchymal cells results in activation of the p38/MK2/Hsp25 signaling pathway downstream from the BMP receptors. Moreover, chemical inhibition of p38 signaling or genetic ablation of either p38α or MK2 blocks the ability to activate the downstream effectors of the pathway and abolishes BMP-2-induction of cell migration. These signaling effects on p38/MK2/Hsp25 do not require the activity of either Cdc42 or PAK, whereas p38/MK2 activities do not significantly modify the BMP-2-dependent activation of LIMK1, measured by either kinase activity or with an antibody raised against phospho-threonine 508 at its activation loop. Finally, phosphorylated Hsp25 colocalizes with the BMP receptor complexes in lamellipodia and overexpression of a phosphorylation mutant form of Hsp25 is able to abolish the migration of cells in response to BMP-2. Conclusions These results indicate that Cdc42/PAK/LIMK1 and p38/MK2/Hsp25 pathways, acting in parallel and modulating specific actin regulatory proteins, play a critical role in integrating responses during BMP-induced actin reorganization and cell migration.

CDC42

BMPR2

Lamellipodium

10.1371/journal.pone.0016477

Cite

Citations (41)

Simposio: enfermedades del páncreas. Apoyo nutricio en pancreatitis aguda grave ¿es útil?

Humberto Arenas Márquez José Luís Rosa Alejandro González‐Ojeda Fernando López Neblina Claudia Lopez

Source

Cite

Citations (0)

TSC1 Stabilizes TSC2 by Inhibiting the Interaction between TSC2 and the HERC1 Ubiquitin Ligase

Journal of Biological Chemistry (2006)

Huira C. Kopera Ken Inoki Yong Li Tianqing Zhu Francesc R. Garcia‐Gonzalo

Tuberous sclerosis complex (TSC) is an autosomal dominant disease characterized by hamartoma formation in various organs. Two genes responsible for the disease, TSC1 and TSC2, have been identified. The TSC1 and TSC2 proteins, also called hamartin and tuberin, respectively, have been shown to regulate cell growth through inhibition of the mammalian target of rapamycin pathway. TSC1 is known to stabilize TSC2 by forming a complex with TSC2, which is a GTPase-activating protein for the Rheb small GTPase. We have identified HERC1 as a TSC2-interacting protein. HERC1 is a 532-kDa protein with an E3 ubiquitin ligase homology to E6AP carboxyl terminus (HECT) domain. We observed that the interaction of TSC1 with TSC2 appears to exclude TSC2 from interacting with HERC1. Disease mutations in TSC2, which result in its destabilization, allow binding to HERC1 in the presence of TSC1. Our study reveals a potential molecular mechanism of how TSC1 stabilizes TSC2 by excluding the HERC1 ubiquitin ligase from the TSC2 complex. Furthermore, these data reveal a possible biochemical basis of how certain disease mutations inactivate TSC2.

TSC1

TSC2

RHEB

10.1074/jbc.c500451200

Cite

Citations (225)