Expression and function of Tec, Itk and Btk in lymphocytes: evidence for a unique role for Tec

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Expression and function of Tec, Itk and Btk in lymphocytes: evidence for a unique role for Tec. / Tomlinson, Michael; Kane, L; Su, J; Kadlecek, TA; Mollenauer, MN; Weiss, A.

In: Molecular and Cellular Biology, Vol. 24, No. 6, 15.03.2004, p. 2455-2466.

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Tomlinson, Michael ; Kane, L ; Su, J ; Kadlecek, TA ; Mollenauer, MN ; Weiss, A. / Expression and function of Tec, Itk and Btk in lymphocytes: evidence for a unique role for Tec. In: Molecular and Cellular Biology. 2004 ; Vol. 24, No. 6. pp. 2455-2466.

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@article{ba466019b12f4e88bfc6a658d2d956bb,
title = "Expression and function of Tec, Itk and Btk in lymphocytes: evidence for a unique role for Tec",
abstract = "The Tec protein tyrosine kinase is the founding member of a family that includes Btk, Itk, Bmx, and Txk. Btk is essential for B-cell receptor signaling, because mutations in Btk are responsible for X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (xid) in mice, whereas Itk is involved in T-cell receptor signaling. Tec is expressed in both T and B cells, but its role in antigen receptor signaling is not clear. In this study, we show that Tec protein is expressed at substantially lower levels in primary T and B cells relative to Itk and Btk, respectively. However, Tec is up-regulated upon T-cell activation and in Th1 and Th2 cells. In functional experiments that mimic Tec up-regulation, we find that Tec overexpression in lymphocyte cell lines is sufficient to induce phospholipase Cgamma (PLC-gamma) phosphorylation and NFAT (nuclear factor of activated T cells) activation. In contrast, overexpression of Btk, Itk, or Bmx does not induce NFAT activation. Tec-induced NFAT activation requires PLC-gamma, but not the adapters LAT, SLP-76, and BLNK, which are required for Btk and Itk to couple to PLC-gamma. Finally, we show that the unique effector function for Tec correlates with a unique subcellular localization. We hypothesize that Tec functions in activated and effector T lymphocytes to induce the expression of genes regulated by NFAT transcription factors.",
author = "Michael Tomlinson and L Kane and J Su and TA Kadlecek and MN Mollenauer and A Weiss",
year = "2004",
month = mar,
day = "15",
doi = "10.1128/MCB.24.6.2455-2466.2004",
language = "English",
volume = "24",
pages = "2455--2466",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "6",

}

RIS

TY - JOUR

T1 - Expression and function of Tec, Itk and Btk in lymphocytes: evidence for a unique role for Tec

AU - Tomlinson, Michael

AU - Kane, L

AU - Su, J

AU - Kadlecek, TA

AU - Mollenauer, MN

AU - Weiss, A

PY - 2004/3/15

Y1 - 2004/3/15

N2 - The Tec protein tyrosine kinase is the founding member of a family that includes Btk, Itk, Bmx, and Txk. Btk is essential for B-cell receptor signaling, because mutations in Btk are responsible for X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (xid) in mice, whereas Itk is involved in T-cell receptor signaling. Tec is expressed in both T and B cells, but its role in antigen receptor signaling is not clear. In this study, we show that Tec protein is expressed at substantially lower levels in primary T and B cells relative to Itk and Btk, respectively. However, Tec is up-regulated upon T-cell activation and in Th1 and Th2 cells. In functional experiments that mimic Tec up-regulation, we find that Tec overexpression in lymphocyte cell lines is sufficient to induce phospholipase Cgamma (PLC-gamma) phosphorylation and NFAT (nuclear factor of activated T cells) activation. In contrast, overexpression of Btk, Itk, or Bmx does not induce NFAT activation. Tec-induced NFAT activation requires PLC-gamma, but not the adapters LAT, SLP-76, and BLNK, which are required for Btk and Itk to couple to PLC-gamma. Finally, we show that the unique effector function for Tec correlates with a unique subcellular localization. We hypothesize that Tec functions in activated and effector T lymphocytes to induce the expression of genes regulated by NFAT transcription factors.

AB - The Tec protein tyrosine kinase is the founding member of a family that includes Btk, Itk, Bmx, and Txk. Btk is essential for B-cell receptor signaling, because mutations in Btk are responsible for X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (xid) in mice, whereas Itk is involved in T-cell receptor signaling. Tec is expressed in both T and B cells, but its role in antigen receptor signaling is not clear. In this study, we show that Tec protein is expressed at substantially lower levels in primary T and B cells relative to Itk and Btk, respectively. However, Tec is up-regulated upon T-cell activation and in Th1 and Th2 cells. In functional experiments that mimic Tec up-regulation, we find that Tec overexpression in lymphocyte cell lines is sufficient to induce phospholipase Cgamma (PLC-gamma) phosphorylation and NFAT (nuclear factor of activated T cells) activation. In contrast, overexpression of Btk, Itk, or Bmx does not induce NFAT activation. Tec-induced NFAT activation requires PLC-gamma, but not the adapters LAT, SLP-76, and BLNK, which are required for Btk and Itk to couple to PLC-gamma. Finally, we show that the unique effector function for Tec correlates with a unique subcellular localization. We hypothesize that Tec functions in activated and effector T lymphocytes to induce the expression of genes regulated by NFAT transcription factors.

UR - http://www.scopus.com/inward/record.url?scp=1542284064&partnerID=8YFLogxK

U2 - 10.1128/MCB.24.6.2455-2466.2004

DO - 10.1128/MCB.24.6.2455-2466.2004

M3 - Article

C2 - 14993283

VL - 24

SP - 2455

EP - 2466

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 6

ER -