Showing papers by "Oliviero Carugo published in 2009"

A Mek1-Mek2 heterodimer determines the strength and duration of the Erk signal.

Abstract: Mek1 and Mek2 (also known as Map2k1 and Map2k2, respectively) are evolutionarily conserved, dual-specificity kinases that mediate Erk1 and Erk2 activation during adhesion and growth factor signaling. Here we describe a previously uncharacterized, unexpected role of Mek1 in downregulating Mek2-dependent Erk signaling. Mek1 mediates the regulation of Mek2 in the context of a previously undiscovered Mek1-Mek2 complex. The Mek heterodimer is negatively regulated by Erk-mediated phosphorylation of Mek1 on Thr292, a residue missing in Mek2. Disabling this Erk-proximal negative-feedback step stabilizes the phosphorylation of both Mek2 and Erk in cultured cells and in vivo in Mek1 knockout embryos and mice. Thus, in disagreement with the current perception of the pathway, the role of Mek1 and Mek2 in growth factor-induced Erk phosphorylation is not interchangeable. Our data establish Mek1 as the crucial modulator of Mek and Erk signaling and have potential implications for the role of Mek1 and Mek2 in tumorigenesis.

Data Mining Techniques for the Life Sciences

Abstract: Whereas getting exact data about living systems and sophisticated experimental procedures have primarily absorbed the minds of researchers previously, the development of high-throughput technologies has caused the weight to increasingly shift to the problem of interpreting accumulated data in terms of biological function and biomolecular mechanisms. In "Data Mining Techniques for the Life Sciences", experts in the field contribute valuable information about the sources of information and the techniques used for "mining" new insights out of databases. Beginning with a section covering the concepts and structures of important groups of databases for biomolecular mechanism research, the book then continues with sections on formal methods for analyzing biomolecular data and reviews of concepts for analyzing biomolecular sequence data in context with other experimental results that can be mapped onto genomes. As a volume of the highly successful Methods in Molecular Biology series, this work provides the kind of detailed description and implementation advice that is crucial for getting optimal results. Authoritative and easy to reference, "Data Mining Techniques for the Life Sciences" seeks to aid students and researchers in the life sciences who wish to get a condensed introduction into the vital world of biological databases and their many applications.

From autoinhibition to inhibition in trans: the Raf-1 regulatory domain inhibits Rok-alpha kinase activity.

Abstract: The activity of Raf-1 and Rok-α kinases is regulated by intramolecular binding of the regulatory region to the kinase domain. Autoinhibition is relieved upon binding to the small guanosine triphosphatases Ras and Rho. Downstream of Ras, Raf-1 promotes migration and tumorigenesis by antagonizing Rok-α, but the underlying mechanism is unknown. In this study, we show that Rok-α inhibition by Raf-1 relies on an intermolecular interaction between the Rok-α kinase domain and the cysteine-rich Raf-1 regulatory domain (Raf-1reg), which is similar to Rok-α's own autoinhibitory region. Thus, Raf-1 mediates Rok-α inhibition in trans, which is a new concept in kinase regulation. This mechanism is physiologically relevant because Raf-1reg is sufficient to rescue all Rok-α–dependent defects of Raf-1–deficient cells. Downstream of Ras and Rho, the Raf-1–Rok-α interaction represents a novel paradigm of pathway cross talk that contributes to tumorigenesis and cell motility.

CARON--average RMSD of NMR structure ensembles.

Abstract: The NMR protein structures are often deposited in the Protein Data Bank as ensembles of models that agree with the experimental restraints. Information about stereochemical variability and the molecular flexibility can be obtained by systematic comparison of all models. Here we describe CARON, a software that allows the computation of the root-mean-square-distances between equivalent atoms and residues in all models and introduces these values into the occupancy and the B-factor fields of PDB-formatted files. This tool allows the user to both get a quantitative estimation of the conformational homogeneity of the models and to exploit this information in common computer graphics programs.

From autoinhibition to inhibition in trans: the Raf-1 regulatory domain inhibits Rok-alpha kinase activity

Abstract: The activity of Raf-1 and Rok-α kinases is regulated by intramolecular binding of the regulatory region to the kinase domain. Autoinhibition is relieved upon binding to the small guanosine triphosphatases Ras and Rho. Downstream of Ras, Raf-1 promotes migration and tumorigenesis by antagonizing Rok-α, but the underlying mechanism is unknown. In this study, we show that Rok-α inhibition by Raf-1 relies on an intermolecular interaction between the Rok-α kinase domain and the cysteine-rich Raf-1 regulatory domain (Raf-1reg), which is similar to Rok-α's own autoinhibitory region. Thus, Raf-1 mediates Rok-α inhibition in trans, which is a new concept in kinase regulation. This mechanism is physiologically relevant because Raf-1reg is sufficient to rescue all Rok-α–dependent defects of Raf-1–deficient cells. Downstream of Ras and Rho, the Raf-1–Rok-α interaction represents a novel paradigm of pathway cross talk that contributes to tumorigenesis and cell motility.

Protein Domain Boundary Predictions: A Structural Biology Perspective

Abstract: One of the important fields to apply computational tools for domain boundaries prediction is structural biology. They can be used to design protein constructs that must be expressed in a stable and functional form and must produce diffraction-quality crystals. However, prediction of protein domain boundaries on the basis of amino acid sequences is still very problematical. In present study the performance of several computational approaches are compared. It is ob- served that the statistical significance of most of the predictions is rather poor. Nevertheless, when the right number of domains is correctly predicted, domain boundaries are predicted within very few residues from their real location. It can be concluded that prediction methods cannot be used yet as routine tools in structural biology, though some of them are rather promising.

Comprar Data Mining Techniques for the Life Sciences | Carugo, Oliviero | 9781603272407 | Springer

Abstract: Tienda online donde Comprar Data Mining Techniques for the Life Sciences al precio 99,21 € de Carugo, Oliviero | Eisenhaber, Frank, tienda de Libros de Medicina, Libros de Medicina Familiar y Comunitaria/General - Medicina general