RESUMEN

Spry2 is a molecular modulator of tyrosine kinase receptor signaling pathways that has cancer-type-specific effects. Mammalian Spry2 protein undergoes tyrosine and serine phosphorylation in response to growth factor stimulation. Spry2 expression is distinctly altered in various cancer types. Inhibition of the proteasome functionality results in reduced intracellular Spry2 degradation. Using in vitro and in vivo assays, we show that protein kinase D (PKD) phosphorylates Spry2 at serine 112 and interacts in vivo with the C-terminal half of this protein. Importantly, missense mutation of Ser112 decreases the rate of Spry2 intracellular protein degradation. Either knocking down the expression of all three mammalian PKD isoforms or blocking their kinase activity with a specific inhibitor contributes to the stabilization of Spry2 wild-type protein. Downregulation of CSN3, a component of the COP9/Signalosome that binds PKD, significantly increases the half-life of Spry2 wild-type protein but does not affect the stability of a Spry2 after mutating Ser112 to the non-phosphorylatable residue alanine. Our data demonstrate that both PKD and the COP9/Signalosome play a significant role in control of Spry2 intracellular stability and support the consideration of the PKD/COP9 complex as a potential therapeutic target in tumors where Spry2 expression is reduced.

RESUMEN

A lo largo de la historia las mujeres han luchado por ser incluidas y reconocidas en el desarrollo de la ciencia médica. En la actualidad, las mujeres tienen mayor participación no solo en el estudio y ejercicio de la medicina sino en el liderazgo de diversas áreas médicas. Este artículo ofrece un panorama histórico de las primeras mujeres que formaron parte de la Academia Nacional de Medicina de México, así como una recopilación de la participación de las mujeres en puestos directivos; desde Jefaturas de Departamentos Académicos en la Universidad Nacional Autónoma de México hasta el sector salud

Throughout history women have been fighting to be included and recognized in the development of medical science. Actually, women have more participation not only in the study and practice of medicine, but in the leadership of various medical areas. This article provides a historical review of the first women it formed part of the National Academy of Medicine of Mexico as well as a compilation of the participation of women in management positions, from Headquarters of academic departments at the National Autonomous University of Mexico including health sector

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RESUMEN

Latrophilins represent a subgroup of the adhesion G protein-coupled receptor family, which bind to actin-associated scaffolding proteins. They are expressed in various tissues, suggesting that they might participate in biological processes that are ubiquitous. Here we focus on actin cytoskeleton dynamics to explore the role of latrophilins in mammalian cells. Individual overexpression of each latrophilin isoform comparably increased cell volume while modifying the net profile of F-actin-dependent cell extensions, as evaluated by confocal microscopy analysis. Latrophilin deletion mutants evidenced that direct coupling to the intracellular machinery was a requirement for modulating cell extensions. The association between latrophilins and the actin cytoskeleton was detected by co-immunoprecipitation assays and corroborated with immunocytochemistry analysis. Consistent with the destabilization of F-actin structures, latrophilin isoforms constitutively induced a prominent increase in the activity of actin-depolymerizing factor, cofilin. Intercellular adhesion events stabilized by heterophilic Teneurin-4 trans-interactions disrupted latrophilin colocalization with F-actin and led to an isoform-specific rescue of cell extensions. Thus, we find that the actin cytoskeleton machinery constitutes an important component of constitutive as well as ligand-induced signaling for latrophilins.This article has an associated First Person interview with the first author of the paper.