PKCtheta and Itk functionally interact during primary mouse CD3+ T cell activation.
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.
Thuille
Nikolaus
N
Department for Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria. Nikolaus.Thuille@i-med.ac.at
Lutz-Nicoladoni
Christina
C
Letschka
Thomas
T
Hermann-Kleiter
Natascha
N
Heit
Isabelle
I
Baier
Gottfried
G
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D015153:Blotting, Western; D017252:CD3 Complex / Q000378:metabolism; D049109:Cell Proliferation; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D005434:Flow Cytometry; D018960:Hyaluronan Receptors / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D000074121:Protein Kinase C-theta; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D015533:Transcriptional Activation; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D018960:Hyaluronan Receptors; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D007527:Isoenzymes; D037181:Lectins, C-Type; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta; D011505:Protein-Tyrosine Kinases; D018808:Transcription Factor AP-1; D000099192:CD69 Antigens; C080813:emt protein-tyrosine kinase; C489593:Prkcq protein, mouse