Transmembrane Protein Aptamer Induces Cooperative Signaling by the EPO Receptor and the Cytokine Receptor β-Common Subunit

He, Li; Cohen, Emily B.; Edwards, A.; Xavier-Ferrucio, Juliana; Bugge, Katrine; Federman, Ross S.; Absher, Devin; Myers, R; Kragelund, Birthe B.; Krause, Diane S.; DiMaio, Daniel

doi:10.1016/j.isci.2019.06.027

Cited by 17 publications

(16 citation statements)

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“…Signaling through these receptors and/or receptor complexes demonstrate distinct biological outcomes, while the molecular mechanism of such signaling is mainly unknown. For example, the study of He et al [ 56 ] revealed that in contrast with the active EPOR homodimer, the EPOR/βcR complex does not utilize the cytoplasmic tyrosines for EPOR signaling.…”

Section: Epor/pi3k/akt and Epor/mapk In Non-hematopoietic Tissuesmentioning

confidence: 99%

The Role of PI3K/AKT and MAPK Signaling Pathways in Erythropoietin Signalization

Tóthová

Šemeláková

Solárová

et al. 2021

IJMS

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Erythropoietin (EPO) is a glycoprotein cytokine known for its pleiotropic effects on various types of cells and tissues. EPO and its receptor EPOR trigger signaling cascades JAK2/STAT5, MAPK, and PI3K/AKT that are interconnected and irreplaceable for cell survival. In this article, we describe the role of the MAPK and PI3K/AKT signaling pathways during red blood cell formation as well as in non-hematopoietic tissues and tumor cells. Although the central framework of these pathways is similar for most of cell types, there are some stage-specific, tissue, and cell-lineage differences. We summarize the current state of research in this field, highlight the novel members of EPO-induced PI3K and MAPK signaling, and in this respect also the differences between erythroid and non-erythroid cells.

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Section: Epor/pi3k/akt and Epor/mapk In Non-hematopoietic Tissuesmentioning

confidence: 99%

The Role of PI3K/AKT and MAPK Signaling Pathways in Erythropoietin Signalization

Tóthová

Šemeláková

Solárová

et al. 2021

IJMS

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“…Traptamers that target other receptors have been isolated. For example, DiMaio and co-workers (196,199) set up a screen for transmembrane sequences that induce IL-3-independent proliferation of BaF3 cells engineered to express EpoR, but not parental BaF3 cells lacking EpoR expression. This led to the discovery of traptamers that activate EpoR but not PDGF␤R.…”

Section: Jbc Reviews: Using Short Peptides To Study Large Receptorsmentioning

confidence: 99%

Membrane receptor activation mechanisms and transmembrane peptide tools to elucidate them

Westerfield

Barrera

2020

Journal of Biological Chemistry

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Single-pass membrane receptors contain extracellular domains that respond to external stimuli and transmit information to intracellular domains through a single transmembrane (TM) α-helix. Because membrane receptors have various roles in homeostasis, signaling malfunctions of these receptors can cause disease. Despite their importance, there is still much to be understood mechanistically about how single-pass receptors are activated. In general, single-pass receptors respond to extracellular stimuli via alterations in their oligomeric state. The details of this process are still the focus of intense study, and several lines of evidence indicate that the TM domain (TMD) of the receptor plays a central role. We discuss three major mechanistic hypotheses for receptor activation: ligand-induced dimerization, ligand-induced rotation, and receptor clustering. Recent observations suggest that receptors can use a combination of these activation mechanisms and that technical limitations can bias interpretation. Short peptides derived from receptor TMDs, which can be identified by screening or rationally developed on the basis of the structure or sequence of their targets, have provided critical insights into receptor function. Here, we explore recent evidence that, depending on the target receptor, TMD peptides cannot only inhibit but also activate target receptors and can accommodate novel, bifunctional designs. Furthermore, we call for more sharing of negative results to inform the TMD peptide field, which is rapidly transforming into a suite of unique tools with the potential for future therapeutics.

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“…Transmembrane Proteins (TMPs), as an essential type of Membrane Proteins(MPs), span the entire biological membrane with segments exposed to both inside and outside of the lipid bilayers (Stillwell 2016). Since TMPs play numerous roles in basic physiology and pathophysiology (Puder, Fischer, and Mierke 2019;He et al 2019;Oguro and Imaoka 2019), they are major targets for nearly half of the known drugs on the current therapeutics market. In the field of drug development, for one thing, interaction information of TMPs helps researchers understand the drug interactions on a molecular biology level, leading the drug design more accurate and efficient (Lee et al 2007).…”

Section: Introductionmentioning

confidence: 99%

TMPs Interaction Domain: A Discovery of Structural Universality Among TMPs Interaction Sites Using Deep Learning Method

Wang

Ming

et al. 2021

Preprint

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Transmembrane proteins (TMPs) serve as important drug targets and accounts for nearly half of the drugs currently available in the market. Research into TMPs interactions and their structural basis will provide key information for drug research and new drug development. Based on previous works like a binding pocket or binding site, our main purpose in this study is to find whether the structural universality (Interaction Domain) exists in all kinds of TMPs interaction regions through a computational approach. After implementing the experiments using our 3D deep learning model and achieve the Matthews correlation coefficient (MCC) of 0.36, we found strong evidence for the existence of the structural basis among TMPs interaction regions. That means those regions, or we call them interaction domains, are structural specific distinguishing to the domains without any interaction. According to this, this work provides a new theoretical basis for TMPs interaction research and can greatly boost the development of the drug industry.

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Transmembrane Protein Aptamer Induces Cooperative Signaling by the EPO Receptor and the Cytokine Receptor β-Common Subunit

Cited by 17 publications

References 58 publications

The Role of PI3K/AKT and MAPK Signaling Pathways in Erythropoietin Signalization

The Role of PI3K/AKT and MAPK Signaling Pathways in Erythropoietin Signalization

Membrane receptor activation mechanisms and transmembrane peptide tools to elucidate them

TMPs Interaction Domain: A Discovery of Structural Universality Among TMPs Interaction Sites Using Deep Learning Method

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