scholarly journals Proteome Microarray Screening Identifies Human Polyphosphate-Binding Proteins in the Phosphatidylinositol Signaling Pathway

2021 ◽  
Author(s):  
Viola Krenzlin ◽  
Julian Roewe ◽  
Marcel Strueve ◽  
María Martínez-Negro ◽  
Christoph Reinhardt ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Intracellular Signaling ◽  
Binding Proteins ◽  
Mammalian Species ◽  
Titration Calorimetry ◽  
Molecular Binding ◽  
Novel Proteins ◽  
Binding Partners ◽  
Linear Chains ◽  
Microarray Screening

AbstractPolyphosphates are linear chains of orthophosphate residues that are present in all living cells. Polyphosphates are released from platelet d-granules and are also produced in bacteria. Polyphosphates are procoagulant in mammalian species and in bacteria are required for energy and phosphate storage, stress resistance, chelation of metal ions and escaping host immunity. Despite these pleiotropic effects, sparse information is available on molecular binding partners of polyphosphates. Here, we used a slide-based human proteome microarray screen for the search of polyphosphate-binding proteins. This approach suggested several novel proteins with relation to the phosphatidylinositol signaling pathway. The highest signals were obtained for Disabled-1 (DAB1) and phosphatidylinositol-5-phosphate 4-kinase 2B (PIP4K2B). Isothermal titration calorimetry was used for confirmation of DAB1 interactions with long-chain polyphosphates. These results offer new rationale to further investigate the interference of polyphosphates with intracellular signaling pathways.

scholarly journals Inhibition of the phosphoinositide 3-kinase-AKT-cyclic GMP-c-Jun N-terminal kinase signaling pathway attenuates the development of morphine tolerance in a mouse model of neuropathic pain

2021 ◽  
Vol 17 ◽  
pp. 174480692110033
Author(s):  
Travis Okerman ◽  
Taylor Jurgenson ◽  
Madelyn Moore ◽  
Amanda H Klein
Keyword(s):  
Spinal Cord ◽  
Sciatic Nerve ◽  
Signaling Pathway ◽  
Intracellular Signaling ◽  
Morphine Tolerance ◽  
Spinal Nerve ◽  
Intracellular Signaling Pathway ◽  
Spinal Cord Dorsal ◽  
Phosphoinositide 3 Kinase ◽  
Induced Tolerance

Research presented here sought to determine if opioid induced tolerance is linked to activity changes within the PI3Kγ-AKT-cGMP-JNK intracellular signaling pathway in spinal cord or peripheral nervous systems. Morphine or saline injections were given subcutaneously twice a day for five days (15 mg/kg) to male C57Bl/6 mice. A separate cohort of mice received spinal nerve ligation (SNL) one week prior to the start of morphine tolerance. Afterwards, spinal cord, dorsal root ganglia, and sciatic nerves were isolated for quantifying total and phosphorylated- JNK levels, cGMP, and gene expression analysis of Pik3cg, Akt1, Pten, and nNos1. This pathway was downregulated in the spinal cord with increased expression in the sciatic nerve of morphine tolerant and morphine tolerant mice after SNL. We also observed a significant increase in phosphorylated- JNK levels in the sciatic nerve of morphine tolerant mice with SNL. Pharmacological inhibition of PI3K or JNK, using thalidomide, quercetin, or SP600125, attenuated the development of morphine tolerance in mice with SNL as measured by thermal paw withdrawal. Overall, the PI3K/AKT intracellular signaling pathway is a potential target for reducing the development of morphine tolerance in the peripheral nervous system. Continued research into this pathway will contribute to the development of new analgesic drug therapies.

THE ROLE OF AGONISTS AND ANTAGONISTS OF THE WNT SIGNALING PATHWAY IN PATIENTS WITH ANDROGENIC ALOPECIA AND ALOPECIA AREATA

2021 ◽  
pp. 87-95
Author(s):  
Samoylova A.V. ◽  
Snimshchikova I.A. ◽  
Plotnikova M.O. ◽  
Yakushkina N.Y.
Keyword(s):  
Wnt Signaling ◽  
Hair Follicle ◽  
Signaling Pathway ◽  
Alopecia Areata ◽  
Intracellular Signaling ◽  
Wnt Signaling Pathway ◽  
Follicle Cells ◽  
Androgenic Alopecia ◽  
Active Population

Alopecia is a common pathology among the active population, which leads not only to cosmetic defects, but also to the development of somatic diseases against the background of traumatic effects and chronic stress. The pathogenetic mechanisms of hair follicle formation are complex and diverse, since numerous factors, including the components of the Wnt signaling pathway, have an effect on its morphogenesis, the study of which is the subject of this study. The search for possible early markers of the development of alopecia led to interest in the study of the main morphogenic proteins of WNT - the signaling pathway (one of the intracellular signaling pathways, which control the development of blood vessels, as well as the growth and division of hair follicle cells) sclerostin and β-catenin among patients with androgenic and alopecia areata. The article presents data on the quantitative content of β-catenin and sclerostin in the blood serum in patients with androgenic and alopecia areata. Their possible pathways of complex interaction and influence on the morphogenesis of the hair follicle and the activity of the Wnt-signaling pathway have been analyzed, and the relationship between changes in the level of morphogenic proteins of the WNT-signaling pathway with sex and the course of the disease has been described. Establishment of the prognostic role of morphogenic proteins of the WNT signaling pathway in androgenic and alopecia areata will allow not only identify the personal risk of disease progression and to determine approaches to targeted therapy, but to develop and introduce updated diagnostic screening into dermatological practice.

scholarly journals Intracellular Signaling Pathway Activation via TGF-β Differs in the Anterior and Posterior Axis During Palatal Development

2016 ◽  
Vol 25 (2) ◽  
pp. 195-204
Author(s):  
Arisa Higa ◽  
Kyoko Oka ◽  
Michiko Kira-Tatsuoka ◽  
Shougo Tamura ◽  
Satoshi Itaya ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Intracellular Signaling ◽  
Intracellular Signaling Pathway ◽  
Pathway Activation ◽  
Palatal Development

scholarly journals Insulin-stimulated GLUT4 Translocation Is Mediated by a Divergent Intracellular Signaling Pathway

1995 ◽  
Vol 270 (47) ◽  
pp. 27991-27994 ◽  
Author(s):  
Tetsuro Haruta ◽  
Aaron J. Morris ◽  
David W. Rose ◽  
James G. Nelson ◽  
Michael Mueckler ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Intracellular Signaling ◽  
Glut4 Translocation ◽  
Intracellular Signaling Pathway

The Role of miRNAs in PI3K Signaling Pathway in Blood Malignancies: A Review Article

2021 ◽  
Author(s):  
Haniyeh Gaffari-Nazari ◽  
Samira Karami ◽  
Leila Noorazar ◽  
Sayeh Parkhideh ◽  
Elham Roshandel ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Signaling Pathway ◽  
Intracellular Signaling ◽  
Pi3k Pathway ◽  
Pi3k Signaling ◽  
Laboratory Findings ◽  
A Cell ◽  
Pi3k Signaling Pathway ◽  
Relationship Of

Background: The PI3K/Akt/mTOR signaling pathway is one of the most important intracellular signaling pathways by regulating the cell cycle process. The direct relationship of this pathway with important mechanisms such as cell quiescence, longevity, and proliferation has been established. The overactive PI3K pathway with decreased and increased apoptosis and cell proliferation respectively is involved in pathogenesis of many cancers, including blood malignancies such as leukemia. Methods: Laboratory findings have shown that different factors, such as miRNAs, play a role in regulating PI3K signaling pathway. These molecules can alter the fate of a cell by interfering in suppression/overexpression of mRNA, transcription factors or stimulating the transcription of some genes. In this article, we reviewed the role of miRNAs in regulating the PI3K/Akt/mTOR pathway and its effect on leukemic progression and treatment failure. Conclusion: At present, miRNAs are known to be one of the causes of treatment failure and relapse in cancers.

scholarly journals Intracellular signaling pathway to prevent caspase activation in osteoclasts.

1999 ◽  
Vol 79 ◽  
pp. 278
Author(s):  
Mitsue Shibata ◽  
Kazuhiro Kanaoka ◽  
Yasuhiro Kobayashi ◽  
Yuzo Kato ◽  
Hideaki Sakai
Keyword(s):  
Signaling Pathway ◽  
Intracellular Signaling ◽  
Caspase Activation ◽  
Intracellular Signaling Pathway

scholarly journals Binding partner- and force-promoted changes in αE-catenin conformation probed by native cysteine labeling

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ksenia Terekhova ◽  
Sabine Pokutta ◽  
Yee S. Kee ◽  
Jing Li ◽  
Emad Tajkhorshid ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Binding Protein ◽  
Binding Domain ◽  
Actin Binding ◽  
Titration Calorimetry ◽  
Allosteric Coupling ◽  
Actin Binding Protein ◽  
Binding Partners ◽  
Actin Binding Domain ◽  
Cysteine Labeling

Abstract Adherens Junctions (AJs) are cell-cell adhesion complexes that sense and propagate mechanical forces by coupling cadherins to the actin cytoskeleton via β-catenin and the F-actin binding protein αE-catenin. When subjected to mechanical force, the cadherin•catenin complex can tightly link to F-actin through αE-catenin, and also recruits the F-actin-binding protein vinculin. In this study, labeling of native cysteines combined with mass spectrometry revealed conformational changes in αE-catenin upon binding to the E-cadherin•β-catenin complex, vinculin and F-actin. A method to apply physiologically meaningful forces in solution revealed force-induced conformational changes in αE-catenin when bound to F-actin. Comparisons of wild-type αE-catenin and a mutant with enhanced vinculin affinity using cysteine labeling and isothermal titration calorimetry provide evidence for allosteric coupling of the N-terminal β-catenin-binding and the middle (M) vinculin-binding domain of αE-catenin. Cysteine labeling also revealed possible crosstalk between the actin-binding domain and the rest of the protein. The data provide insight into how binding partners and mechanical stress can regulate the conformation of full-length αE-catenin, and identify the M domain as a key transmitter of conformational changes.

scholarly journals Intrinsic elasticity of nucleosomes is encoded by histone variants and calibrated by their binding partners

2019 ◽  
Vol 116 (48) ◽  
pp. 24066-24074 ◽  
Author(s):  
Daniël P. Melters ◽  
Mary Pitman ◽  
Tatini Rakshit ◽  
Emilios K. Dimitriadis ◽  
Minh Bui ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Chromosome Segregation ◽  
Binding Proteins ◽  
Histone Variants ◽  
Histone Variant ◽  
Binding Partners ◽  
Damage Repair ◽  
Fine Tune

Histone variants fine-tune transcription, replication, DNA damage repair, and faithful chromosome segregation. Whether and how nucleosome variants encode unique mechanical properties to their cognate chromatin structures remains elusive. Here, using in silico and in vitro nanoindentation methods, extending to in vivo dissections, we report that histone variant nucleosomes are intrinsically more elastic than their canonical counterparts. Furthermore, binding proteins, which discriminate between histone variant nucleosomes, suppress this innate elasticity and also compact chromatin. Interestingly, when we overexpress the binding proteins in vivo, we also observe increased compaction of chromatin enriched for histone variant nucleosomes, correlating with diminished access. Taken together, these data suggest a plausible link between innate mechanical properties possessed by histone variant nucleosomes, the adaptability of chromatin states in vivo, and the epigenetic plasticity of the underlying locus.

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