Positive regulation of Itk PH domain function by soluble IP4 is required for thymocyte positive selection but dispensable for negative selection

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Delineation of signals required for thymocyte positive selection.

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B-Raf is required for positive selection and survival of DP cells, but not for negative selection of SP cells.

The duration of signaling through the MAP kinase (or ERK pathway) cascade has been implicated in thymic development, particularly positive and negative selection. In T cells, two isoforms of the MAP kinase kinase kinase Raf function to transmit signals from the T-cell receptor to ERK: C-Raf and B-Raf. In this study, we conditionally ablated B-Raf expression within thymocytes to assess the effec...

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The Absence of Itk Inhibits Positive Selection

The Tec family tyrosine kinase Itk is critical for efficient signaling downstream of the TCR. Biochemically, Itk is directly phos-phorylated and activated by Lck. Subsequently, Itk activates phospholipase C-␥1, leading to calcium mobilization and extracel-lular signal-regulated kinase/mitogen-activated protein kinase activation. These observations suggested that Itk might play an important role...

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A molecular chart of thymocyte positive selection.

As a new slant on T lymphocyte repertoire selection, we have examined batteries of TCR sequences in thymi from transgenic mice engineered to exhibit limited, focussed TCR diversity. We have tracked the fate of differentiating thymocytes expressing a set of particular TCR through the positive selection process. Subtly different TCR sequences can promote different maturation pathways and commitme...

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Protein Kinase C- Is Required for Efficient Positive Selection

Protein kinase C(PKC ) is critical for TCR-initiated signaling in mature T cells, but initial reports found no requirement for PKC in thymocyte development. Thymocytes and peripheral T cells utilize many of the same signaling components and, given the significant role of PKC in peripheral T cells, it was surprising that it was not involved at all in TCR signaling in thymocytes. We decided to re...

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ژورنال

عنوان ژورنال: The FASEB Journal

سال: 2008

ISSN: 0892-6638,1530-6860

DOI: 10.1096/fasebj.22.1_supplement.843.8