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FBW7 mutations in leukemic cells mediate NOTCH pathway activation and resistance to γ-secretase inhibitors
TLDR
It is shown that all seven leukemic cell lines with FBW7 mutations were resistant to the MRK-003 GSI and most of these resistant lines also failed to down-regulate the mRNA levels of the NOTCH targets MYC and DELTEX1 after treatment with MRk-003, implying that residual NOTCH signaling in T-ALLs with FBw7 mutations contributes to GSI resistance. Expand
Inhibition of NOTCH signaling by gamma secretase inhibitor engages the RB pathway and elicits cell cycle exit in T-cell acute lymphoblastic leukemia cells.
TLDR
Investigation of the mechanisms of GSI sensitivity across a panel of T-ALL cell lines yielded an approach for patient stratification based on pathway activity and a rational combination strategy for enhanced response to GSI, providing evidence that GSI engagement of the CDK4/RB pathway is an important mechanism of G SI action. Expand
Suppression of immunoglobulin E–mediated allergic responses by regulator of G protein signaling 13
TLDR
It is shown that RGS13 inhibited allergic responses by physically interacting with the regulatory p85α subunit of phosphatidylinositol-3-OH kinase in mast cells and disrupting its association with an FcεRI-activated scaffolding complex. Expand
Cutting Edge: Interleukin 4-Dependent Mast Cell Proliferation Requires Autocrine/Intracrine Cysteinyl Leukotriene-Induced Signaling1
TLDR
IL-4 induces proliferation in part by inducing LTC4S and cys-LT generation, which causes CysLT1 to transactivate c-kit in RM, and IL-4-driven comitogenesis was likewise sensitive to pertussis toxin or a Cys LT1-selective antagonist and was attenuated by treatment with leukotriene synthesis inhibitors. Expand
RGS13 Controls G Protein-Coupled Receptor-Evoked Responses of Human Mast Cells1
TLDR
Results suggest that RGS13 restricts certain GPCR-mediated biological responses of human mast cells, including Ca2+ mobilization, Akt phosphorylation and chemotaxis. Expand
RGS13 controls g protein-coupled receptor-evoked responses of human mast cells.
TLDR
Results suggest that RGS13 restricts certain GPCR-mediated biological responses of human mast cells, including Ca(2+) mobilization, Akt phosphorylation and chemotaxis. Expand
Modulation of signaling proteins in cultured mast cells from chronic idiopathic urticaria patients
Abstract Rationale Although mast cells and basophils have been implicated in the generation of urticarial lesions, signaling changes in the FceRI pathway are unexplored. In the present study, weExpand
Targeting Notch in cancer with gamma-secretase inhibitors
TLDR
In vitro and in vivo models of T-ALL and other solid tumors have been developed to explore the mechanism of action of gamma-secretase inhibitors and to study the correlation pathway inhibition and anti-tumor efficacy. Expand
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