A novel functional interaction between Vav and PKCtheta is required for TCR-induced T cell activation.
Vav and PKCtheta play an early and important role in the TCR/CD28-induced stimulation of MAP kinases and activation of the IL-2 gene. Vav is also essential for actin cytoskeleton reorganization and TCR capping. Here, we report that PKCtheta function was selectively required in a Vav signaling pathway that mediates the TCR/CD28-induced activation of JNK and the IL-2 gene and the upregulation of CD69 expression. Vav also promoted PKCtheta translocation from the cytosol to the membrane and cytoskeleton and induced its enzymatic activation in a CD3/CD28-initiated pathway that was dependent on Rac and on actin cytoskeleton reorganization. These findings reveal that the Vav/Rac pathway promotes the recruitment of PKCtheta to the T cell synapse and its activation, essential processes for T cell activation and IL-2 production.
Villalba
M
M
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA.
Coudronniere
N
N
Deckert
M
M
Teixeiro
E
E
Mas
P
P
Altman
A
A
D000199:Actins / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D001692:Biological Transport; D018106:CD28 Antigens / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002462:Cell Membrane / Q000378:metabolism; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics; D007527:Isoenzymes / Q000378:metabolism* / Q000502:physiology; D048031:JNK Mitogen-Activated Protein Kinases; D019169:Jurkat Cells; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism* / Q000502:physiology; D000074121:Protein Kinase C-theta; D011518:Proto-Oncogene Proteins / Q000378:metabolism* / Q000502:physiology; D051567:Proto-Oncogene Proteins c-vav; D011817:Rabbits; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*; D015533:Transcriptional Activation; D015854:Up-Regulation; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D000099192:CD69 Antigens
D000199:Actins; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D018797:Cell Cycle Proteins; D007376:Interleukin-2; D007527:Isoenzymes; D048031:JNK Mitogen-Activated Protein Kinases; D037181:Lectins, C-Type; D020928:Mitogen-Activated Protein Kinases; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta; D011518:Proto-Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; D011948:Receptors, Antigen, T-Cell; D020744:rac GTP-Binding Proteins; D000099192:CD69 Antigens; C496618:VAV1 protein, human; C076233:PRKCQ protein, human