Inositol (1,4,5) trisphosphate 3 kinase B controls positive selection of T cells and modulates Erk activity

Wen, Ben G.; Pletcher, Mathew T.; Warashina, Masaki; Choe, Sun Hui; Ziaee, Niusha; Wiltshire, Tim; Sauer, Karsten; Cooke, M.

doi:10.1073/pnas.0306907101

Cited by 73 publications

(155 citation statements)

References 54 publications

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“…ϩ stage during thymocyte development, indicating an essential role for Itpkb in T cell development (12,13). More recently, we and others have established that Itpkb is also essential for B cell development, selection, and activation (14,15).…”

Section: Cd8mentioning

confidence: 99%

Inositol 1,4,5-Trisphosphate 3-Kinase B Is a Negative Regulator of BCR Signaling That Controls B Cell Selection and Tolerance Induction

Miller

Beisner²,

Liu³

et al. 2009

The Journal of Immunology

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Inositol 1,4,5-trisphosphate 3-kinase B (or Itpkb) converts inositol 1,4,5-trisphosphate to inositol 1,3,4,5-tetrakisphosphate upon Ag receptor activation and controls the fate and function of lymphocytes. To determine the role of Itpkb in B cell tolerance, Itpkb−/− mice were crossed to transgenic mice that express a BCR specific for hen egg lysozyme (IgHEL). B cells from Itpkb−/− IgHEL mice possess an anergic phenotype, hypoproliferate in response to cognate Ag, and yet they exhibit enhanced Ag-induced calcium signaling. In IgHEL transgenic mice that also express soluble HEL, lack of Itpkb converts anergy induction to deletion. These data establish Itpkb as a negative regulator of BCR signaling that controls the fate of developing B cells and tolerance induction.

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Section: Cd8mentioning

confidence: 99%

Inositol 1,4,5-Trisphosphate 3-Kinase B Is a Negative Regulator of BCR Signaling That Controls B Cell Selection and Tolerance Induction

Miller

Beisner²,

Liu³

et al. 2009

The Journal of Immunology

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“…The absolute number of lymphocytes in peripheral blood was reduced significantly in the InsP3KB knockout mice. [9][10][11][12] However, intriguingly, disruption of InsP3KB resulted in elevated peripheral blood neutrophil count, indicating an augmentation of neutrophil production from bone marrow. Fluorescence-Activated Cell-sorting (FACS) analysis of bone marrow cells revealed an elevation of granulocyte monocytes progenitors (GMP) population in the knockout mice.…”

Section: Ins(1345)p4 and Insp3kb Regulate Innate Immunity Via Modumentioning

confidence: 99%

“…Surprisingly, in InsP3KB null T cells, no substantial defects in Ins(1,4,5)P3 amounts or calcium mobilization was detected. 9,10 In neutrophils, disruption of InsP3KB does not affect the overall calcium signaling in the presence of extracellular calcium. 16 However, more detailed investigation revealed a much decreased calcium release from intracellular store and an enhanced calcium influx through store-operated calcium channels in InsP3KB null neutrophils stimulated with chemokines.…”

Section: Ins(1345)p4 and Insp3kb Regulate Innate Immunity Via Modumentioning

confidence: 99%

“…In addition, the amounts of mature B-and T-cells are dramatically decreased in the InsP3KB knockout mice, resulting in reduction of the serum level of IgG which is essential for opsinization and phagocytosis. [9][10][11][12] We conducted an in vitro bacteria killing assay using purified neutrophils and serum from wild-type and InsP3KB knockout mice (Fig. 2B).…”

Section: Bacterial Killing In Insp3kb Deficient Micementioning

confidence: 99%

“…Two independent studies showed that disruption of InsP3KB led to dramatic decrease of cellular Ins(1,3,4,5)P4 level, impaired T cell development, and defective thymocyte selection. 9,10 Disruption of InsP3KB also induces B cell death and impaired B cell development. 11,12 In addition, we recently showed that InsP3KB is the major InsP3K isoform in neutrophils.…”

Section: Introductionmentioning

confidence: 99%

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Regulation of innate immunity by inositol 1,3,4,5-tetrakisphosphate

2008

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Phosphoinositide and Inositol Phosphate Analysis in Lymphocyte Activation

et al. 2009

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Lymphocyte antigen receptor engagement profoundly changes the cellular content of phosphoinositide lipids and soluble inositol phosphates. Among these, the phosphoinositides phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol 3,4,5-trisphosphate (PIP3) play key signaling roles by acting as pleckstrin homology (PH) domain ligands that recruit signaling proteins to the plasma membrane. Moreover, PIP2 acts as a precursor for the second messenger molecules diacylglycerol and soluble inositol 1,4,5-trisphosphate (IP3), essential mediators of PKC, Ras/Erk, and Ca2+ signaling in lymphocytes. IP3 phosphorylation by IP3 3-kinases generates inositol 1,3,4,5-tetrakisphosphate (IP4), an essential soluble regulator of PH domain binding to PIP3 in developing T cells. Besides PIP2, PIP3, IP3, and IP4, lymphocytes produce multiple other phosphoinositides and soluble inositol phosphates that could have important physiological functions. To aid their analysis, detailed protocols that allow one to simultaneously measure the levels of multiple different phosphoinositide or inositol phosphate isomers in lymphocytes are provided here. They are based on thin layer, conventional and high-performance liquid chromatographic separation methods followed by radiolabeling or non-radioactive metal-dye detection. Finally, less broadly applicable nonchromatographic methods for detection of specific phosphoinositide or inositol phosphate isomers are discussed. Support protocols describe how to obtain pure unstimulated CD4+CD8+ thymocyte populations for analyses of inositol phosphate turnover during positive and negative selection, key steps in T cell development.

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Inositol (1,4,5) trisphosphate 3 kinase B controls positive selection of T cells and modulates Erk activity

Cited by 73 publications

References 54 publications

Inositol 1,4,5-Trisphosphate 3-Kinase B Is a Negative Regulator of BCR Signaling That Controls B Cell Selection and Tolerance Induction

Inositol 1,4,5-Trisphosphate 3-Kinase B Is a Negative Regulator of BCR Signaling That Controls B Cell Selection and Tolerance Induction

Regulation of innate immunity by inositol 1,3,4,5-tetrakisphosphate

Phosphoinositide and Inositol Phosphate Analysis in Lymphocyte Activation

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