Growth Hormone Receptor Signaling Pathways and its Negative Regulation by SOCS2

Growth hormone (GH) is a critical regulator of linear body growth during childhood but continues to have important metabolic actions throughout life. The GH receptor (GHR) is ubiquitously expressed, and deficiency of GHR signaling causes a dramatic impact on normal physiology during somatic development, adulthood, and aging. GHR belongs to a family of receptors without intrinsic kinase activity. However, GH binding to homodimers of GHR results in a conformational change in the receptors and the associated tyrosine kinase Janus kinase 2 (JAK2) molecules. Activated JAK2 phosphorylates the GHR cytoplasmic domain on tyrosine residues, and subsequent JAK2-dependent and JAK2-independent intracellular signal transduction pathways evoke cell responses including changes in gene transcription, proliferation, cytoskeletal reorganization, and lipid and glucose metabolism. JAK2 phosphorylates STAT5b, which is a key transcription factor in GH regulation of target genes associated with body growth, intermediate metabolism, and gender dimorphism; although STAT1, 3, and 5a have also been shown to be recruited by the GHR. In addition, many transcripts are regulated independently of STAT5b as a result of GHR activation of Src, ERK, and PI3K-mTOR signaling pathways. The analysis of molecular mechanisms involved in inactivation of GHR-dependent signaling pathway is also imperative for understanding GH physiology. This is clearly illustrated in the case of hepatic GHR-JAK2-STAT5b activation where signal duration regulates gender differences in liver gene expression. An early step in the termination of GH-dependent signaling is removal of GHRs by endocytosis and ubiquitination. The level of ubiquitin ligase SOCS2 is constitutively low, but its expression is rapidly induced by GH. SOCS2 binding to GHR complex promotes their ubiquitination and subsequent proteasomal degradation, contributing to the termination of the GH intracellular signaling. Clinically relevant, SOCS2 is a key negative regulator of GH-dependent body growth and lipid and glucose homeostasis. Furthermore, several cytokines, growth factors, xenobiotics, and sex hormones can regulate SOCS2 protein level, which provides a mechanism for cross-talking where multiple factors can regulate GHR signaling during somatic development. A better understanding of this complex regulation in physiological and pathological states will contribute to prevent health damage and improve clinical management of patients with growth and metabolic disorders

Religación. Revista de Ciencias Sociales y Humanidades (Vol. 1 no. 2 abr-jun 2016)

Religación. Revista de Ciencias Sociales y Humanidades, es una revista académica de periodicidad trimestral, editada por el Centro de Investigaciones en Ciencias Sociales y Humanidades desde América Latina, centro asociado a CLACSO. Revista Religación, pretende ser un espacio abierto para el debate y construcción del pensamiento latinoamericano en el campo de las Ciencias Sociales y Humanidades, destinado a profesionales, investigadores, estudiantes y académicos que tengan interés en el estudio de la realidad de nuestra Abya Yala con un enfoque decolonizador. Se encarga de difundir trabajos científicos de investigación producidos por los diferentes grupos de trabajo del Centro de Investigaciones, así como trabajos de investigadores nacionales e internacionales externos. Tiene su sede en Quito, Ecuador, maneja áreas que tienen relación con la: Ciencia Política, Educación, Religión, Filosofía, Antropología, Sociología, Historia y otras afines.Presentación Roberto Simbaña Q Dossier: Subjetivaciones y Nuevas Emancipaciones Políticas en América Latina La chispa de la participación política: Historias de mujeres mapuce durante el conflicto Pulmarí. Suyai Malen García Gualda Os estudantes ainda estão famintos!: ousadia, ocupação e resistência dos estudantes secundaristas no Brasil Denise N. De Sordi, Sérgio Paulo Morais Réplica a El desafío de las políticas educativas de subjetividad de Juan Carlos Tedesco. Una propuesta de integración de los procesos de subjetivación Armando Ulises Cerón Martínez La subjetividad como punto de reflexión teórica para pensar lo polí- tico Juan M. Fernández Chico A aprendizagem duma segunda cultura e a identidade étnica dos indí- genas brasileiros através duma rede social: estudo exploratório Joaquim Filipe Peres de Castro Ensayo Fotográfico Rendered visible. A photographic document Michael Wildman, Carolina Borda-Niño-Wildman Sección General El murmullo de la cultura: semiótica y sentido de la vida Massimo Leone Calidad de la educación: entre la exclusión y la utopía Adriana Bojacá I., Alejandra Díaz L., Rafael Osorio O. y Juan Carlos Muñoz C. Normas para presentación de artículo

The Canfranc Axion Detection Experiment (CADEx): Search for axions at 90 GHz with Kinetic Inductance Detectors

We propose a novel experiment, the Canfranc Axion Detection Experiment (CADEx), to probe dark matter axions with masses in the range 330-460 $\mu$eV, within the W-band (80-110 GHz), an unexplored parameter space in the well-motivated dark matter window of Quantum ChromoDynamics (QCD) axions. The experimental design consists of a microwave resonant cavity haloscope in a high static magnetic field coupled to a highly sensitive detecting system based on Kinetic Inductance Detectors via optimized quasi-optics (horns and mirrors). The experiment is in preparation and will be installed in the dilution refrigerator of the Canfranc Underground Laboratory. Sensitivity forecasts for axion detection with CADEx, together with the potential of the experiment to search for dark photons, are presented.Comment: 23 pages, 10 figure