Compte M, Cuesta AM, Sánchez-Martín D, Camino VA, Vicario JL, Sanz L, Alvarez-Vallina L.

" Tumor Immunotherapy using Gene-Modified Human Mesenchymal Stem Cells Loaded into Synthetic Extracellular Matrix Scaffolds."

Más Información en http://stemcells.alphamedpress.org/cgi/r...

Sanz L, Cuesta AM, Salas C, Corbacho C, Bellas C, Alvarez-Vallina L.

"Differential transplantability of human endothelial cells in colorectal cancer and renal cell carcinoma primary xenografts."

Más Información en http://www.nature.com/labinvest/journal/...

Larsen M, Jensen KB, Christensen PA, Suarez E, Paris D, Sanz L, Ravn P, Sauce D, Saas P, Goletz S, Alvarez-Vallina L, Kristensen P.

"Functionally fused antibodies-A novel adjuvant fusion system. J Immunol Methods. 2008 Dec 31;339(2):220-7."

Más Información en http://www.sciencedirect.com/science?_ob...

Cuesta AM, Sánchez-Martín D, Sanz L, Alvarez-Vallina L.

"Production of multivalent protein binders using a self-trimerization collagen-like peptide scaffold"

Más Información en http://www.ncbi.nlm.nih.gov/pubmed/18827...

Sanz L, Santos-Valle P, Alonso-Camino V, Salas C, Serrano A, Vicario JL,Cuesta AM, Compte M, Sánchez-Martín D, Alvarez-Vallina L.

"Long-term in vivo imaging of human angiogenesis: critical role of bone marrow-derived mesenchymal stem cells for the generation of durable blood vessels."

Más Información en http://www.sciencedirect.com/science?_ob...

Martínez-Torrecuadrada JL, Cheung LH, López-Serra P, Barderas R, Cañamero M, Ferreiro S, Rosenblum MG, Casal JI.

"Antitumor activity of fibroblast growth factor receptor 3-specific immunotoxins in a xenograft mouse model of bladder carcinoma is mediated by apoptosis. Mol Cancer Ther. 2008 Apr;7(4):862-73. "

Barderas R, Shochat S, Timmerman P, Hollestelle MJ, Martínez-Torrecuadrada JL, Höppener JW, Altschuh D, Meloen R, Casal JI.

" Designing antibodies for the inhibition of gastrin activity in tumoral cell lines. Int J Cancer. 2008 May 15;122(10):2351-9. "

Munera D., Palomino C., and L.A. Fernández

""Specific residues in the N-terminal domain of FimH stimulate type 1 fimbriae assembly in Escherichia coli following the initial binding of the adhesin to FimD usher ”Molecular Microbiology 2008; 69: 911-925."

Más Información en http://www3.interscience.wiley.com/journ...

Demuth, A., Aharonowitz, Y., Bachmann, T. T., Blum-Oehler, G.Buchrieser, C., Covacci, A., Dobrindt, U., Emody, L., van der Ende, A., Ewbank, J., Fernández, L. A., et al.

"" Pathogenomics: an updated European Research Agenda” Infection, Genetics and Evolution 2008; 8: 386-393."

Más Información en http://www.sciencedirect.com/science?_ob...

Martínez-Martínez S, Genescà L, Rodríguez A, Raya A, Salichs E, Were F, López-Maderuelo MD, Redondo JM, de la Luna S.

"The RCAN carboxyl-end mediates calcineurin docking-dependent inhibition via a site that dictates binding to substrates and regulators. Proc Natl Acad Sci U S A. 2009 Apr 14;106(15):6117-22. Epub 2009 Mar 30."

Specificity of signaling kinases and phosphatases toward their targets is usually mediated by docking interactions with substrates and regulatory proteins. Here, we characterize the motifs involved in the physical and functional interaction of the phosphatase calcineurin with one group of modulators, the RCAN protein family. Mutation of key residues within the hydrophobic docking-cleft of the calcineurin catalytic domain impairs binding to all human RCAN proteins and to the calcineurin interacting proteins Cabin1 and AKAP79. A valine-rich region within the RCAN carboxyl-region is essential for binding to the docking site in calcineurin. Although a peptide containing this sequence compromises NFAT signaling in living cells, it does not inhibit calcineurin catalytic activity directly. Instead, calcineurin catalytic activity is inhibited by a motif at the extreme C-terminal region of RCAN, which acts in cis with the docking motif. Our results therefore indicate that the inhibitory action of RCAN on calcineurin-NFAT signaling results not only from the inhibition of phosphatase activity, but also from competition between NFAT and RCAN for binding to the same docking site in calcineurin. Thus competition by substrates and modulators for a common docking site appears to be an essential mechanism in the regulation of Ca2+-calcineurin signaling.

Más Información en http://www.pnas.org/content/106/15/6117....

Rodríguez A, Roy J, Martínez-Martinez S, López-Maderuelo MD, Nińo-Moreno P, Ortí L, Pantoja-Uceda D, Pineda-Lucena A, Cyert MS, Redondo JM.

"A conserved docking surface on calcineurin mediates interaction with substrates and immunosuppressants. Mol Cell. 2009 Mar 12; 33(5)"

The phosphatase calcineurin, target of the immunosuppressants cyclosporin A and FK506, dephosphorylates NFAT transcription factors to promote immune activation and development of the vascular and nervous systems. NFAT interacts with calcineurin through distinct binding motifs: the PxIXIT and LxVP sites. While many calcineurin substrates contain PxIxIT motifs, the generality of LxVP-mediated interactions is unclear. We define critical residues in the LxVP motif, and demonstrate its binding to a hydrophobic pocket at the interface of the two calcineurin subunits. Mutations in this region disrupt binding of mammalian calcineurin to NFATc1, and interaction of yeast calcineurin with substrates including Rcn1, which contains an LxVP motif. These mutations also interfere with calcineurin immunosuppressant binding, and an LxVP-based peptide competes with immunosuppressant-immunophilin complexes for binding to calcineurin. These studies suggest that LxVP-type sites are a common feature of calcineurin substrates and that immunosuppressant-immunophilin complexes inhibit calcineurin by interfering with this mode of substrate recognition.

Más Información en http://www.cell.com/molecular-cell/retri...