AKT1/PKBalpha is recruited to lipid rafts and activated downstream of PKC isotypes in CD3-induced T cell signaling.
Protein kinase (PK) Ctheta and Akt/PKBalpha cooperate in T cell receptor/CD28-induced T cell signaling. We here demonstrate the recruitment of endogenous Akt1 and PKCtheta to lipid rafts in CD3-stimulated T cells. Further we show that Myr-PKCtheta mediates translocation of endogenous Akt1 to the plasma membrane as well as to lipid rafts, most likely explained by the observed complex formation of both protein kinases. In addition, in peripheral mouse T cells, the PKC inhibitor Gö6850 could partially block Akt1 activation in CD3-induced signaling, placing PKC isotype(s) upstream of Akt1. However, T cells derived from PKCtheta knockout mice were not impaired in CD3- or phorbol ester-induced Akt1 activity. Taken together, the results of this study give new insights into the functional link of Akt1 and PKCtheta in T cell signaling, demonstrating the co-recruitment of the two kinases and showing a novel pathway leading to Akt1 transactivation where PKC isotype(s) are involved but PKCtheta is not essential.
Bauer
Birgit
B
Department of Medical Biology and Human Genetics, University of Innsbruck, Austria.
Jenny
Marcel
M
Fresser
Fiedrich
F
Uberall
Florian
F
Baier
Gottfried
G
D000818:Animals; D018106:CD28 Antigens / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism*; D002462:Cell Membrane / Q000201:enzymology; D004789:Enzyme Activation; D006801:Humans; D007527:Isoenzymes / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D019169:Jurkat Cells; D021962:Membrane Microdomains / Q000201:enzymology*; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D011493:Protein Kinase C / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D000074121:Protein Kinase C-theta; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology
D018106:CD28 Antigens; D017252:CD3 Complex; D007527:Isoenzymes; D011518:Proto-Oncogene Proteins; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; C076233:PRKCQ protein, human; C489593:Prkcq protein, mouse; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta