Extracellular signal-regulated kinases

Résumé

Les protéines ERK1/2 sont des enzymes, des kinases, qui ajoutent des groupements phosphate à d'autres protéines afin de les activer. ERK1/2 font partie de la famille des MAP kinases qui sont des protéines jouant un rôle dans la division, la croissance et la prolifération cellulaires. Généralités Les protéines ERK-1 et ERK-2 signifiant Extracellular signal-regulated kinases sont des protéines codées par les gènes 16p11.2 pour ERK-1 et 22p11.2 pour ERK-2. Ce sont deux isoformes respectivement de poids moléculaires de 43 kDa (379 acides aminés) et 41 kDa (360 acides aminés) chez l’humain. Quand ces protéines deviennent phosphorylées, elles acquièrent un poids moléculaire de 44 kDa et 42 kDa respectivement pour ERK-1 et pour ERK-2. Bien que ERK-1 et ERK-2 possèdent plusieurs autres noms (voir tableau 1), les chercheurs les nomment couramment ERK1/2. Ces deux enzymes ont un degré d’homologie de 83 %, car on remarque une similitude dans la séquence et la composition de leurs

Source officielle

https://fr.wikipedia.org/wiki/Extracellular_signal-regulated_kinases

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, ,

The Shc family of adaptor proteins are crucial mediators of a plethora of receptors such as the tyrosine kinase receptors, cytokine receptors, and integrins that drive signaling pathways governing proliferation, differentiation, and migration. Here, we report the role of the newly identified family member, ShcD/RaLP, whose expression in vitro and in vivo suggests a function in embryonic stem cell (ESC) to epiblast stem cells (EpiSCs) transition. The transition from the naive (ESC) to the primed (EpiSC) pluripotent state is the initial important step for ESCs to commit to differentiation and the mechanisms underlying this process are still largely unknown. Using a novel approach to simultaneously assess pluripotency, apoptosis, and proliferation by multiparameter flow cytometry, we show that ESC to EpiSC transition is a process involving a tight coordination between the modulation of the Oct4 expression, cell cycle progression, and cell death. We also describe, by high-content immunofluorescence analysis and time-lapse microscopy, the emergence of cells expressing caudal-related homeobox 2 (Cdx2) transcription factor during ESC to EpiSC transition. The use of the ShcD knockout ESCs allowed the unmasking of this process as they presented deregulated Oct4 modulation and an enrichment in Oct4-negative Cdx2-positive cells with increased MAPK/extracellular-regulated kinases 1/2 activation, within the differentiating population. Collectively, our data reveal ShcD as an important modulator in the switch of key pathway(s) involved in determining EpiSC identity. STEM CELLS2012;30:24232436

Wiley-Blackwell2012

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Patterning and shaping the endoderm in vivo and in culture

Anne Grapin-Botton, Marine Marie Kraus

The definitive endoderm (DE) was first defined as the innermost germ layer found in all metazoan embryos. During development, it gives rise to a vast array of specialized epithelial cell types lining the respiratory and digestive systems, and contributes to associated organs such as thyroid, thymus, lungs, liver, and pancreas. In the adult, the DE provides a protective barrier against the environment and assumes many essential functions including digestion, nutrient absorption, and glucose homeostasis. Since general endoderm formation and patterning have been reviewed recently in a comprehensive manner [1], we will only provide a brief summary of how extracellular signals and downstream transcription factors control endoderm patterning. We will then focus on emerging work addressing the chromatin remodeling events occurring during endoderm organ specification and discuss how these molecular tools can be used to engineer endodermal organs in vitro.

Elsevier2012

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Intravital Immunofluorescence for Visualizing the Microcirculatory and Immune Microenvironments in the Mouse Ear Dermis

Witold Waldemar Kilarski, Amanda Waite Lund, Scott Oliver, Melody Swartz, Jeremy Teo

Visualizing the dynamic behaviors of immune cells in living tissue has dramatically increased our understanding of how cells interact with their surroundings, contributing important insights into mechanisms of leukocyte trafficking, tumor cell invasion, and T cell education by dendritic cells, among others. Despite substantial advances with various intravital imaging techniques including two-photon microscopy and the generation of multitudes of reporter mice, there is a growing need to assess cell interactions in the context of specific extracellular matrix composition and microvascular functions, and as well, simpler and more widely accessible methods are needed to image cell behaviors in the context of living tissue physiology. Here we present an antibody-based method for intravital imaging of cell interactions with the blood, lymphatic, and the extracellular matrix compartments of the living dermis while simultaneously assessing capillary permeability and lymphatic drainage function. Using the exposed dorsal ear of the anesthetized mouse and a fluorescence stereomicroscope, such events can be imaged in the context of specific extracellular matrix proteins, or matrix-bound chemokine stores. We developed and optimized the method to minimize tissue damage to the ear, rapidly immunostain for multiple extracellular or cell surface receptors of interest, minimize immunotoxicity with pre-blocking Fc gamma receptors and phototoxicity with extracellular antioxidants, and highlight the major dermal tissue structures with basement membrane markers. We demonstrate differential migration behaviors of bone marrow-derived dendritic cells, blood-circulating leukocytes, and dermal dendritic cells, with the latter entering sparse CCL21-positive areas of pre-collecting lymphatic vessels. This new method allows simultaneous imaging of cells and tissue structures, microvascular function, and extracellular microenvironment in multiple skin locations for 12 hours or more, with the flexibility of immunolabeling in addition to genetic-based fluorescent reporters.

Public Library of Science2013

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Intravital Immunofluorescence for Visualizing the Microcirculatory and Immune Microenvironments in the Mouse Ear Dermis

Witold Waldemar Kilarski, Amanda Waite Lund, Scott Oliver, Melody Swartz, Jeremy Teo

Public Library of Science2013