PKCtheta and Itk functionally interact during primary mouse CD3+ T cell activation

Immunol Lett. 2009 Sep 22;126(1-2):54-9. doi: 10.1016/j.imlet.2009.07.014. Epub 2009 Aug 12.


PKCtheta serine/threonine and Itk tyrosine protein kinases have been implicated in T lymphocyte signal transmission. We observed a PKCtheta/Itk complex after T cell activation, raising the possibility that PKCtheta and Itk might interact functionally during T cell development and response. To address this question PKCtheta/Itk double knockout mice were generated and T cell activation responses were compared to single deficiencies as well as to wild type controls. Consistent with previous reports, Itk and PKCtheta are required in modulating CD3(+) T cell cytokine secretion responses ex vivo. Itk- and PKCtheta-deficient cells show impaired NFAT/AP-1 and NF-kappaB transactivation responses, however the combined loss, did not exceed but partially rescue the strong NFAT and NF-kappaB activation defects observed in Itk(-/-) single-deficient T cells. Taken together, this provides evidence for a more complex functional crosstalk between Itk and PKCtheta during T cell receptor signalling then previously anticipated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • Blotting, Western
  • CD3 Complex / metabolism
  • Cell Proliferation
  • Electrophoretic Mobility Shift Assay
  • Female
  • Flow Cytometry
  • Hyaluronan Receptors / metabolism
  • Interleukin-2 / metabolism
  • Interleukin-2 Receptor alpha Subunit / metabolism
  • Isoenzymes / genetics
  • Isoenzymes / metabolism*
  • Lectins, C-Type
  • Lymphocyte Activation*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NF-kappa B / metabolism
  • NFATC Transcription Factors / metabolism
  • Phosphorylation
  • Protein Binding
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism*
  • Protein Kinase C-theta
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / metabolism*
  • Transcription Factor AP-1 / metabolism
  • Transcriptional Activation


  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD3 Complex
  • CD69 antigen
  • Hyaluronan Receptors
  • Interleukin-2
  • Interleukin-2 Receptor alpha Subunit
  • Isoenzymes
  • Lectins, C-Type
  • NF-kappa B
  • NFATC Transcription Factors
  • Transcription Factor AP-1
  • Protein-Tyrosine Kinases
  • emt protein-tyrosine kinase
  • Prkcq protein, mouse
  • Protein Kinase C
  • Protein Kinase C-theta