10 research outputs found

    Registered Ship Notes

    Get PDF
    https://digitalmaine.com/blue_hill_documents/1179/thumbnail.jp

    Strategies for Multiplexed Biosensor Imaging to Study Intracellular Signaling Networks.

    No full text
    Signal transduction processes are a necessary component of multicellular life, and their dysregulation is the basis for a host of syndromes and diseases. Thus, it is imperative that we discover the complex details of how signal transduction processes result in specific cellular outcomes. One of the primary mechanisms of regulation over signaling pathways is through spatiotemporal control. However, traditional methods are limited in their ability to reveal such details. To overcome these limitations, researchers have developed a variety of genetically encodable, fluorescent protein-based biosensors to study these dynamic processes in real time in living cells. Due to the complexities and interconnectedness of signaling pathways, it is thus desirable to use multiple biosensors in individual cells to better elucidate the relationships between signaling pathways. However, multiplexed imaging with such biosensors has been historically difficult. Nevertheless, recent developments in designs and multiplexing strategies have led to vast improvements in our capabilities. In this review, we provide perspectives on the recently developed biosensor designs and multiplexing strategies that are available for multiplexed imaging of signal transduction pathways

    Endogenous, regulatory cysteine sulfenylation of ERK kinases in response to proliferative signals.

    No full text
    ERK-dependent signaling is key to many pathways through which extracellular signals are transduced into cell-fate decisions. One conundrum is the way in which disparate signals induce specific responses through a common, ERK-dependent kinase cascade. While studies have revealed intricate ways of controlling ERK signaling through spatiotemporal localization and phosphorylation dynamics, additional modes of ERK regulation undoubtedly remain to be discovered. We hypothesized that fine-tuning of ERK signaling could occur by cysteine oxidation. We report that ERK is actively and directly oxidized by signal-generated

    Hydrogen peroxide-dependent oxidation of ERK2 within its D-recruitment site alters its substrate selection

    No full text
    Summary: Extracellular signal-regulated kinases 1 and 2 (ERK1/2) are dysregulated in many pervasive diseases. Recently, we discovered that ERK1/2 is oxidized by signal-generated hydrogen peroxide in various cell types. Since the putative sites of oxidation lie within or near ERK1/2’s ligand-binding surfaces, we investigated how oxidation of ERK2 regulates interactions with the model substrates Sub-D and Sub-F. These studies revealed that ERK2 undergoes sulfenylation at C159 on its D-recruitment site surface and that this modification modulates ERK2 activity differentially between substrates. Integrated biochemical, computational, and mutational analyses suggest a plausible mechanism for peroxide-dependent changes in ERK2-substrate interactions. Interestingly, oxidation decreased ERK2’s affinity for some D-site ligands while increasing its affinity for others. Finally, oxidation by signal-generated peroxide enhanced ERK1/2’s ability to phosphorylate ribosomal S6 kinase A1 (RSK1) in HeLa cells. Together, these studies lay the foundation for examining crosstalk between redox- and phosphorylation-dependent signaling at the level of kinase-substrate selection

    Registered Ship Notes

    Get PDF
    https://digitalmaine.com/blue_hill_documents/1179/thumbnail.jp
    corecore