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Sökning: WFRF:(Mikoshiba K)

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  • Zhang, SB, et al. (författare)
  • GIT1 protects against breast cancer growth through negative regulation of Notch
  • 2022
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 1537-
  • Tidskriftsartikel (refereegranskat)abstract
    • Hyperactive Notch signalling is frequently observed in breast cancer and correlates with poor prognosis. However, relatively few mutations in the core Notch signalling pathway have been identified in breast cancer, suggesting that as yet unknown mechanisms increase Notch activity. Here we show that increased expression levels of GIT1 correlate with high relapse-free survival in oestrogen receptor-negative (ER(-)) breast cancer patients and that GIT1 mediates negative regulation of Notch. GIT1 knockdown in ER(-) breast tumour cells increased signalling downstream of Notch and activity of aldehyde dehydrogenase, a predictor of poor clinical outcome. GIT1 interacts with the Notch intracellular domain (ICD) and influences signalling by inhibiting the cytoplasm-to-nucleus transport of the Notch ICD. In xenograft experiments, overexpression of GIT1 in ER(-) cells prevented or reduced Notch-driven tumour formation. These results identify GIT1 as a modulator of Notch signalling and a guardian against breast cancer growth.
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  • Miyakawa-Naito, A., et al. (författare)
  • Cell signaling Microdomain with Na,K-ATPase and inositol 1,4,5-trisphosphate receptor generates calcium oscillations
  • 2003
  • Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 17:4, s. A43-A43
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent studies indicate novel roles for the ubiquitous ion pump, Na,K-ATPase, in addition to its function as a key regulator of intracellular sodium and potassium concentration. We have previously demonstrated that ouabain, the endogenous ligand of Na, K-ATPase, can trigger intracellular Ca2+ oscillations, a versatile intracellular signal controlling a diverse range of cellular processes. Here we report that Na, K-ATPase and inositol 1,4,5-trisphosphate (InsP(3)) receptor (InsP(3)R) form a cell signaling microdomain that, in the presence of ouabain, generates slow Ca2+ oscillations in renal cells. Using fluorescent resonance energy transfer ( FRET) measurements, we detected a close spatial proximity between Na, K-ATPase and InsP(3)R. Ouabain significantly enhanced FRET between Na, K-ATPase and InsP(3)R. The FRET effect and ouabain-induced Ca2+ oscillations were not observed following disruption of the actin cytoskeleton. Partial truncation of the NH2 terminus of Na, K-ATPase catalytic alpha1-subunit abolished Ca2+ oscillations and downstream activation of NF-kappaB. Ouabain-induced Ca2+ oscillations occurred in cells expressing an InsP3 sponge and were hence independent of InsP3 generation. Thus, we present a novel principle for a cell signaling microdomain where an ion pump serves as a receptor.
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  • Resultat 1-8 av 8

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