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
N1 - Funding Information:
We thank Nicole Bem and Susan Magargee at Penn State and Rod Getchell at Cornell for technical support with flow cytometry and confocal microscopy, and Victor Tse at Cornell for help with luciferase activity assay. We also thank Dr. Maurine E. Linder in Department of Molecular Medicine at Cornell University for critical comments on the manuscript and members in August lab for comments and feedback. This work was supported by grant from the National Institutes of Health ( AI051626 and AI065566 to A.A.).
PY - 2013/6
Y1 - 2013/6
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.
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U2 - 10.1016/j.biocel.2013.02.011
DO - 10.1016/j.biocel.2013.02.011
M3 - Article
C2 - 23454662
AN - SCOPUS:84875932262
SN - 1357-2725
VL - 45
SP - 1074
EP - 1082
JO - International Journal of Biochemistry and Cell Biology
JF - International Journal of Biochemistry and Cell Biology
IS - 6
ER -