Overexpression of ICAT highlights a rolefor catenin-mediated canonical Wnt signalling in early T cell development

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Overexpression of ICAT highlights a rolefor catenin-mediated canonical Wnt signalling in early T cell development. / Pongracz, JE; Parnell, Sonia; Jones, T; Anderson, Graham; Jenkinson, Eric.

In: European Journal of Immunology, Vol. 36, No. 9, 01.09.2006, p. 2376-83.

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@article{c0c9f33e4c5f46fba067242dcfbbbe4d,
title = "Overexpression of ICAT highlights a rolefor catenin-mediated canonical Wnt signalling in early T cell development",
abstract = "Transcription factors of the T cell factor/lymphoid enhancing factor (Tcf/Lef) family are key regulators in the development of T cell precursors to the CD4(+)8(+) stage. These factors are known targets of the canonical Wnt signalling pathway, and regulate transcription of Wnt target genes following interaction with the armadillo repeat-containing protein beta-catenin. However, as recent studies show normal thymocyte maturation in the absence of either beta-catenin or its homologue gamma-catenin, the role of Wnt signalling in Tcf/Lef activation during T cell development is controversial. To directly investigate the importance of catenin-mediated Wnt signalling in early thymocytes, we have compared the expression of beta- and gamma-catenin and analysed distinct stages of T cell precursor maturation following overexpression of inhibitor of beta-catenin and Tcf (ICAT), which inhibits Wnt signalling by preventing binding of armadillo repeat-containing proteins to Tcf/Lef. By direct retroviral gene targeting of CD4(-)8(-) and CD4(+)8(+) precursors, we show that ICAT overexpression inhibits the CD4(-)8(-)-to-CD4(+)8(+) transition, but not the CD4(+)8(+)-to-CD4(+)8(-) or -CD4(-)8(+) transition. Collectively, our data support a model in which canonical Wnt signalling influences T cell development in the thymus by playing an essential role in the maturation of CD4(-)8(-) but not CD4(+)8(+) thymocytes.",
keywords = "thymopoiesis, cellular immunology, cell differentiation",
author = "JE Pongracz and Sonia Parnell and T Jones and Graham Anderson and Eric Jenkinson",
year = "2006",
month = sep,
day = "1",
doi = "10.1002/eji.200535721",
language = "English",
volume = "36",
pages = "2376--83",
journal = "European Journal of Immunology",
issn = "0014-2980",
publisher = "Wiley-VCH Verlag",
number = "9",

}

RIS

TY - JOUR

T1 - Overexpression of ICAT highlights a rolefor catenin-mediated canonical Wnt signalling in early T cell development

AU - Pongracz, JE

AU - Parnell, Sonia

AU - Jones, T

AU - Anderson, Graham

AU - Jenkinson, Eric

PY - 2006/9/1

Y1 - 2006/9/1

N2 - Transcription factors of the T cell factor/lymphoid enhancing factor (Tcf/Lef) family are key regulators in the development of T cell precursors to the CD4(+)8(+) stage. These factors are known targets of the canonical Wnt signalling pathway, and regulate transcription of Wnt target genes following interaction with the armadillo repeat-containing protein beta-catenin. However, as recent studies show normal thymocyte maturation in the absence of either beta-catenin or its homologue gamma-catenin, the role of Wnt signalling in Tcf/Lef activation during T cell development is controversial. To directly investigate the importance of catenin-mediated Wnt signalling in early thymocytes, we have compared the expression of beta- and gamma-catenin and analysed distinct stages of T cell precursor maturation following overexpression of inhibitor of beta-catenin and Tcf (ICAT), which inhibits Wnt signalling by preventing binding of armadillo repeat-containing proteins to Tcf/Lef. By direct retroviral gene targeting of CD4(-)8(-) and CD4(+)8(+) precursors, we show that ICAT overexpression inhibits the CD4(-)8(-)-to-CD4(+)8(+) transition, but not the CD4(+)8(+)-to-CD4(+)8(-) or -CD4(-)8(+) transition. Collectively, our data support a model in which canonical Wnt signalling influences T cell development in the thymus by playing an essential role in the maturation of CD4(-)8(-) but not CD4(+)8(+) thymocytes.

AB - Transcription factors of the T cell factor/lymphoid enhancing factor (Tcf/Lef) family are key regulators in the development of T cell precursors to the CD4(+)8(+) stage. These factors are known targets of the canonical Wnt signalling pathway, and regulate transcription of Wnt target genes following interaction with the armadillo repeat-containing protein beta-catenin. However, as recent studies show normal thymocyte maturation in the absence of either beta-catenin or its homologue gamma-catenin, the role of Wnt signalling in Tcf/Lef activation during T cell development is controversial. To directly investigate the importance of catenin-mediated Wnt signalling in early thymocytes, we have compared the expression of beta- and gamma-catenin and analysed distinct stages of T cell precursor maturation following overexpression of inhibitor of beta-catenin and Tcf (ICAT), which inhibits Wnt signalling by preventing binding of armadillo repeat-containing proteins to Tcf/Lef. By direct retroviral gene targeting of CD4(-)8(-) and CD4(+)8(+) precursors, we show that ICAT overexpression inhibits the CD4(-)8(-)-to-CD4(+)8(+) transition, but not the CD4(+)8(+)-to-CD4(+)8(-) or -CD4(-)8(+) transition. Collectively, our data support a model in which canonical Wnt signalling influences T cell development in the thymus by playing an essential role in the maturation of CD4(-)8(-) but not CD4(+)8(+) thymocytes.

KW - thymopoiesis

KW - cellular immunology

KW - cell differentiation

U2 - 10.1002/eji.200535721

DO - 10.1002/eji.200535721

M3 - Article

C2 - 16897815

VL - 36

SP - 2376

EP - 2383

JO - European Journal of Immunology

JF - European Journal of Immunology

SN - 0014-2980

IS - 9

ER -