Ezrin is a specific and direct target of protein tyrosine phosphatase PRL-3

AbstractPhosphatase of Regenerating Liver-3 (PRL-3) is a small protein tyrosine phosphatase considered an appealing therapeutic cancer target due to its involvement in metastatic progression. However, despite its importance, the direct molecular targets of PRL-3 action are not yet known. Here we report the identification of Ezrin as a specific and direct cellular substrate of PRL-3. In HCT116 colon cancer cell line, Ezrin was identified among the cellular proteins whose phosphorylation level decreased upon ectopic over-expression of wtPRL-3 but not of catalytically inactive PRL-3 mutants. Although PRL-3 over-expression in HCT116 cells appeared to affect Ezrin phosphorylation status at both tyrosine residues and Thr567, suppression of the endogenous protein by RNA interference pointed to Ezrin-Thr567 as the residue primarily affected by PRL-3 action. In vitro dephosphorylation assays suggested Ezrin-Thr567 as a direct substrate of PRL-3 also proving this enzyme as belonging to the dual specificity phosphatase family. Furthermore, the same effect on levels of pThr567, but not on pTyr residues, was observed in endothelial cells pointing to Ezrin-pThr567 dephosphorylation as a mean through which PRL-3 exerts its function in promoting tumor progression as well as in the establishment of the new vasculature needed for tumor survival and expansion

Platelet-derived Growth Factor Induces the β-γ-Secretase-mediated Cleavage of Alzheimer's Amyloid Precursor Protein through a Src-Rac-dependent Pathway

The beta-amyloid peptide (Abeta) present in the senile plaques of Alzheimer's disease derives from the cleavage of a membrane protein, named APP, driven by two enzymes, known as beta- and gamma-secretases. The mechanisms regulating this cleavage are not understood. We have developed an experimental system to identify possible extracellular signals able to trigger the cleavage of an APP-Gal4 fusion protein, which is detected by measuring the expression of the CAT gene transcribed under the control of the Gal4 transcription factor, which is released from the membrane upon the cleavage of APP-Gal4. By using this assay, we purified a protein contained in the C6 cell-conditioned medium, which activates the cleavage of APP-Gal4 and which we demonstrated to be PDGF-BB. The APP-Gal4 processing induced by PDGF is dependent on the gamma-secretase activity, being abolished by an inhibitor of this enzyme, and is the consequence of the activation of a pathway downstream of the PDGF-receptor, which includes the non-receptor tyrosine kinase Src and the small G-protein Rac1. These findings are confirmed by the observation that a constitutively active form of Src increases Abeta generation and that, in cells stably expressing APP, the generation of A is strongly decreased by the Src tyrosine kinase inhibitor PP2

An infant burial from Arma Veirana in northwestern Italy provides insights into funerary practices and female personhood in early Mesolithic Europe

The evolution and development of human mortuary behaviors is of enormous cultural significance. Here we report a richly-decorated young infant burial (AVH-1) from Arma Veirana (Liguria, northwestern Italy) that is directly dated to 10,211–9910 cal BP (95.4% probability), placing it within the early Holocene and therefore attributable to the early Mesolithic, a cultural period from which well-documented burials are exceedingly rare. Virtual dental histology, proteomics, and aDNA indicate that the infant was a 40–50 days old female. Associated artifacts indicate significant material and emotional investment in the child’s interment. The detailed biological profile of AVH-1 establishes the child as the earliest European near-neonate documented to be female. The Arma Veirana burial thus provides insight into sex/gender-based social status, funerary treatment, and the attribution of personhood to the youngest individuals among prehistoric hunter-gatherer groups and adds substantially to the scant data on mortuary practices from an important period in prehistory shortly following the end of the last Ice Age

Consumo, risparmio, rimesse, Una proposta di analisi

Recentemente è stato affrontato il tema dell'integrazione attraverso i consumi analizzando le strategie messe in atto da cittadini migranti che proprio attraverso l’assimilazione e la riproduzione degli stili di consumo del paese ospitante ricostituiscono, ricompongono o innovano una domanda identitaria culturale comunque percepita come un bisogno più che latente. Il saggio analizza le dinamiche di risparmio, consumo e rimesse dei cittadini migranti con una proposta di analisiRecently, the theme of integration through consumption has been addressed by analyzing the strategies implemented by migrant citizens who, precisely through the assimilation and reproduction of the host country's consumption styles, reconstitute, recompose or innovate a demand for cultural identity perceived as a more than latent need. The essay analyzes the dynamics of savings, consumption, and remittances of migrant citizens with a proposal of analysi

A layered IT infrastructure for secure interoperability in Personal Data . . .

In this paper we describe the architectural solution defined and implemented to ensure secure interoperability among Information Technology (IT) systems managing Personal Data Registries in Italian Municipalities and Ministry of Interior. The architecture features a clear separation between security services, provided at an infrastructure level, and application services, exposed on the Internet as Web Services. This approach has allowed to easily design and implement secure interoperability, since - notwithstanding the huge variety of IT solutions deployed all over the Italian Municipalities to manage Personal Data Registries - existing application services have not required major changes to be able to interoperate

Inter-Organizational E-Services Accounting Management On . . .

Accounting management is of strategic importance for a successful uptake of computational Grid technology within the user community. Computational Grid is one the most important paradigms for distributed computing and high-performance e-service provision. In this paper we present an architecture for accounting management of e-services on computational Grids which fully meets both the reliability and security requirements for accounting management architectures defined by the Internet Engineering Task Force (IETF). The presented solution, based on previous work successfully deployed in many italian public administrations, nicely fits with the overall Grid architectures and features a clear separation between management of the service and its control

Reliable peer-to-peer access for Italian citizens To Digital Government . . .

In the delivery of e-government services to citizens it should be clear that the viewpoint cannot simply be the standard one of client-supplier commonly used to provide services on the Internet. In a modern society it has rather to be the peer-to-peer approach which is typical of democracies, where institutions are equal to citizens in front of the law. But this is not yet a widely accepted standpoint in digital government efforts going on in many advanced countries in the world. Italian governmen