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.
authors: Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853, United States.
authors: Weishan
authors: W
authors: Huang
authors: J Luis
authors: JL
authors: Morales
authors: Victor P
authors: VP
authors: Gazivoda
authors: Jianbin
authors: J
authors: Lai
authors: Qian
authors: Q
authors: Qi
authors: Avery
authors: A
authors: August
mesh_terms: D001665:Binding Sites; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation / Q000502:physiology; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D026362:Serum Response Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*; D015032:Zinc / Q000378:metabolism
chemical_list: D011948:Receptors, Antigen, T-Cell; C476858:SRF protein, human; D026362:Serum Response Factor; D011505:Protein-Tyrosine Kinases; C080813:emt protein-tyrosine kinase; D044365:GTP-Binding Protein alpha Subunits, G12-G13; D015032:Zinc