Phosphatidylinositol-3-Kinase C2β and TRIM27 Function To Positively and Negatively Regulate IgE Receptor Activation of Mast Cells

Srivastava, S. K.; Cai, Xinjiang; Zhai, Li; Sun, Yi; Skolnik, Edward Y.

doi:10.1128/mcb.00019-12

Cited by 28 publications

(34 citation statements)

References 38 publications

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“…Fura-2 fluorescence was recorded (Delta Ram; PTI Inc., South Brunswick, NJ) in an RC-20 bath flow chamber (Warner Instrument Corp., Hamden, CT), at excitation wavelengths of 340 and 380 nm (Srivastava et al, 2012). Data are represented as 340/380 ratios after background subtraction.…”

Section: Methodsmentioning

confidence: 99%

Metabolic Inflexibility Impairs Insulin Secretion and Results In MODY-like Diabetes in Triple FoxO-Deficient Mice

et al. 2014

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Pancreatic β-cell failure in type 2 diabetes is associated with functional abnormalities of insulin secretion and deficits of β-cell mass. It’s unclear how one begets the other. We have shown that loss of β-cell mass can be ascribed to impaired FoxO1 function in different models of diabetes. Here we show that ablation of the three FoxO genes (1, 3a, and 4) in mature β-cells results in early-onset, maturity onset diabetes of the young (MODY)-like diabetes, with abnormalities of the MODY networks of Hnf4α, Hnf1α, and Pdx1. FoxO-deficient β-cells are metabolically inflexible, i.e., they preferentially utilize lipids rather than carbohydrates as an energy source. This results in impaired ATP generation, and reduced Ca2+-dependent insulin secretion. The present findings demonstrate a secretory defect caused by impaired FoxO activity that antedates dedifferentiation. We propose that defects in both pancreatic β–cell function and mass arise through FoxO-dependent mechanisms during diabetes progression.

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Section: Methodsmentioning

confidence: 99%

Metabolic Inflexibility Impairs Insulin Secretion and Results In MODY-like Diabetes in Triple FoxO-Deficient Mice

et al. 2014

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“…TRIM27 also negatively regulates IgE receptor activation and downstream signaling by the same mechanism (49). Further analyses using Trim27 Ϫ/Ϫ mice may help to elucidate the uncharacterized physiological roles of TRIM27.…”

Section: Figmentioning

confidence: 96%

Ubiquitination-Deubiquitination by the TRIM27-USP7 Complex Regulates Tumor Necrosis Factor Alpha-Induced Apoptosis

Zaman

Nomura

Takagi³

et al. 2013

Molecular and Cellular Biology

101

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bTumor necrosis factor alpha (TNF-␣) plays a role in apoptosis and proliferation in multiple types of cells, and defects in TNF-␣-induced apoptosis are associated with various autoimmune diseases. Here, we show that TRIM27, a tripartite motif (TRIM) protein containing RING finger, B-box, and coiled-coil domains, positively regulates TNF-␣-induced apoptosis. Trim27-deficient mice are resistant to TNF-␣-D-galactosamine-induced hepatocyte apoptosis. Trim27-deficient mouse embryonic fibroblasts (MEFs) are also resistant to TNF-␣-cycloheximide-induced apoptosis. TRIM27 forms a complex with and ubiquitinates the ubiquitin-specific protease USP7, which deubiquitinates receptor-interacting protein 1 (RIP1), resulting in the positive regulation of TNF-␣-induced apoptosis. Our findings indicate that the ubiquitination-deubiquitination cascade mediated by the TRIM27-USP7 complex plays an important role in TNF-␣-induced apoptosis.

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“…Similar to CD4 + T cells, in mast cells both PI3K-C2β and NDPK-B function downstream of FcɛRI activation and, along with Ca 2+ -calmodulin binding to the C terminus of K Ca 3.1, are required for K Ca 3.1 activation (347). FcɛRI stimulation of Ca 2+ influx, de-granulation, and cytokine production were attenuated following siRNA knockdown of PI3K-C2β in BMDMCs (347) or in BMDMCs derived from PI3KC2β − / − mice (E. Skolnik, unpublished observation). In addition, both passive systemic and cutaneous anaphylaxis were markedly attenuated in PI3KC2β − / − mice (E. Skolnik, unpublished observation).…”

Section: Ion Channels In Mast Cells and Allergymentioning

confidence: 99%

“…In addition, both passive systemic and cutaneous anaphylaxis were markedly attenuated in PI3KC2β − / − mice (E. Skolnik, unpublished observation). On the flip side, FcɛRI activation of mast cells was markedly enhanced in BMDMCs derived from trim27 − / − mice; TRIM27 negatively regulates PI3K-C2β kinase activity, and in contrast to PI3KC2β − / − mice, trim27 − / − mice exhibit enhanced systemic anaphylaxis (347). The serum and glucocorticoid-inducible kinase (SGK1) is also important in FcɛRI activation of K Ca 3.1 in mast cells (348, 349).…”

Section: Ion Channels In Mast Cells and Allergymentioning

confidence: 99%

Ion Channels in Innate and Adaptive Immunity

Feske¹,

Wulff

Skolnik

2015

Annu. Rev. Immunol.

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600

616

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Ion channels and transporters mediate the transport of charged ions across hydrophobic lipid membranes. In immune cells, divalent cations such as calcium, magnesium, and zinc have important roles as second messengers to regulate intracellular signaling pathways. By contrast, monovalent cations such as sodium and potassium mainly regulate the membrane potential, which indirectly controls the influx of calcium and immune cell signaling. Studies investigating human patients with mutations in ion channels and transporters, analysis of gene-targeted mice, or pharmacological experiments with ion channel inhibitors have revealed important roles of ionic signals in lymphocyte development and in innate and adaptive immune responses. We here review the mechanisms underlying the function of ion channels and transporters in lymphocytes and innate immune cells and discuss their roles in lymphocyte development, adaptive and innate immune responses, and autoimmunity, as well as recent efforts to develop pharmacological inhibitors of ion channels for immunomodulatory therapy.

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Phosphatidylinositol-3-Kinase C2β and TRIM27 Function To Positively and Negatively Regulate IgE Receptor Activation of Mast Cells

Cited by 28 publications

References 38 publications

Metabolic Inflexibility Impairs Insulin Secretion and Results In MODY-like Diabetes in Triple FoxO-Deficient Mice

Metabolic Inflexibility Impairs Insulin Secretion and Results In MODY-like Diabetes in Triple FoxO-Deficient Mice

Ubiquitination-Deubiquitination by the TRIM27-USP7 Complex Regulates Tumor Necrosis Factor Alpha-Induced Apoptosis

Ion Channels in Innate and Adaptive Immunity

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