The zinc-binding region of IL-2 inducible T cell kinase (Itk) is required for interaction with Gα13 and activation of serum response factor

Weishan Huang, J. Luis Morales, Victor P. Gazivoda, Jianbin Lai, Qian Qi, Avery August

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Tec family kinases play critical roles in the activation of immune cells. In particular, Itk is important for the activation of T cells via the T cell Receptor (TcR), however, molecules that cooperate with Itk to activate downstream targets remain little explored. Here we show that Itk interacts with the heterotrimeric G-protein α subunit Gα13 during TcR triggering. This interaction requires membrane localization of both partners, and is partially dependent on GDP- and GTP-bound states of Gα13. Furthermore, we find that Itk interacts with Gα13 via the zinc binding regions within its Tec homology domain. The interaction between Itk and Gα13 also results in tyrosine phosphorylation of Gα13, however this is not required for the interaction. Itk enhances Gα13 mediated activation of serum response factor (SRF) transcriptional activity dependent on its ability to interact with Gα13, but its kinase activity is not required to enhance SRF activity. These data reveal a new pathway regulated by Itk in cells, and suggest cross talk between Itk and G-protein signaling downstream of the TcR.

Original languageEnglish (US)
Pages (from-to)1074-1082
Number of pages9
JournalInternational Journal of Biochemistry and Cell Biology
Volume45
Issue number6
DOIs
StatePublished - Jun 1 2013

Fingerprint

Serum Response Factor
Zinc
Chemical activation
T-Cell Antigen Receptor
Phosphotransferases
Heterotrimeric GTP-Binding Proteins
Phosphorylation
T-cells
emt protein-tyrosine kinase
Protein Subunits
Guanosine Triphosphate
GTP-Binding Proteins
Tyrosine
Membranes
T-Lymphocytes
Molecules

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cell Biology

Cite this

Huang, Weishan ; Morales, J. Luis ; Gazivoda, Victor P. ; Lai, Jianbin ; Qi, Qian ; August, Avery. / The zinc-binding region of IL-2 inducible T cell kinase (Itk) is required for interaction with Gα13 and activation of serum response factor. In: International Journal of Biochemistry and Cell Biology. 2013 ; Vol. 45, No. 6. pp. 1074-1082.
@article{54d8064b829040acafb6954f1e769896,
title = "The zinc-binding region of IL-2 inducible T cell kinase (Itk) is required for interaction with Gα13 and activation of serum response factor",
abstract = "Tec family kinases play critical roles in the activation of immune cells. In particular, Itk is important for the activation of T cells via the T cell Receptor (TcR), however, molecules that cooperate with Itk to activate downstream targets remain little explored. Here we show that Itk interacts with the heterotrimeric G-protein α subunit Gα13 during TcR triggering. This interaction requires membrane localization of both partners, and is partially dependent on GDP- and GTP-bound states of Gα13. Furthermore, we find that Itk interacts with Gα13 via the zinc binding regions within its Tec homology domain. The interaction between Itk and Gα13 also results in tyrosine phosphorylation of Gα13, however this is not required for the interaction. Itk enhances Gα13 mediated activation of serum response factor (SRF) transcriptional activity dependent on its ability to interact with Gα13, but its kinase activity is not required to enhance SRF activity. These data reveal a new pathway regulated by Itk in cells, and suggest cross talk between Itk and G-protein signaling downstream of the TcR.",
author = "Weishan Huang and Morales, {J. Luis} and Gazivoda, {Victor P.} and Jianbin Lai and Qian Qi and Avery August",
year = "2013",
month = "6",
day = "1",
doi = "10.1016/j.biocel.2013.02.011",
language = "English (US)",
volume = "45",
pages = "1074--1082",
journal = "International Journal of Biochemistry and Cell Biology",
issn = "1357-2725",
publisher = "Elsevier Limited",
number = "6",

}

The zinc-binding region of IL-2 inducible T cell kinase (Itk) is required for interaction with Gα13 and activation of serum response factor. / Huang, Weishan; Morales, J. Luis; Gazivoda, Victor P.; Lai, Jianbin; Qi, Qian; August, Avery.

In: International Journal of Biochemistry and Cell Biology, Vol. 45, No. 6, 01.06.2013, p. 1074-1082.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The zinc-binding region of IL-2 inducible T cell kinase (Itk) is required for interaction with Gα13 and activation of serum response factor

AU - Huang, Weishan

AU - Morales, J. Luis

AU - Gazivoda, Victor P.

AU - Lai, Jianbin

AU - Qi, Qian

AU - August, Avery

PY - 2013/6/1

Y1 - 2013/6/1

N2 - Tec family kinases play critical roles in the activation of immune cells. In particular, Itk is important for the activation of T cells via the T cell Receptor (TcR), however, molecules that cooperate with Itk to activate downstream targets remain little explored. Here we show that Itk interacts with the heterotrimeric G-protein α subunit Gα13 during TcR triggering. This interaction requires membrane localization of both partners, and is partially dependent on GDP- and GTP-bound states of Gα13. Furthermore, we find that Itk interacts with Gα13 via the zinc binding regions within its Tec homology domain. The interaction between Itk and Gα13 also results in tyrosine phosphorylation of Gα13, however this is not required for the interaction. Itk enhances Gα13 mediated activation of serum response factor (SRF) transcriptional activity dependent on its ability to interact with Gα13, but its kinase activity is not required to enhance SRF activity. These data reveal a new pathway regulated by Itk in cells, and suggest cross talk between Itk and G-protein signaling downstream of the TcR.

AB - Tec family kinases play critical roles in the activation of immune cells. In particular, Itk is important for the activation of T cells via the T cell Receptor (TcR), however, molecules that cooperate with Itk to activate downstream targets remain little explored. Here we show that Itk interacts with the heterotrimeric G-protein α subunit Gα13 during TcR triggering. This interaction requires membrane localization of both partners, and is partially dependent on GDP- and GTP-bound states of Gα13. Furthermore, we find that Itk interacts with Gα13 via the zinc binding regions within its Tec homology domain. The interaction between Itk and Gα13 also results in tyrosine phosphorylation of Gα13, however this is not required for the interaction. Itk enhances Gα13 mediated activation of serum response factor (SRF) transcriptional activity dependent on its ability to interact with Gα13, but its kinase activity is not required to enhance SRF activity. These data reveal a new pathway regulated by Itk in cells, and suggest cross talk between Itk and G-protein signaling downstream of the TcR.

UR - http://www.scopus.com/inward/record.url?scp=84875932262&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84875932262&partnerID=8YFLogxK

U2 - 10.1016/j.biocel.2013.02.011

DO - 10.1016/j.biocel.2013.02.011

M3 - Article

C2 - 23454662

AN - SCOPUS:84875932262

VL - 45

SP - 1074

EP - 1082

JO - International Journal of Biochemistry and Cell Biology

JF - International Journal of Biochemistry and Cell Biology

SN - 1357-2725

IS - 6

ER -