Membrane translocation of protein kinase Ctheta during T lymphocyte activation requires phospholipase C-gamma-generated diacylglycerol.
Protein kinase C (PKC) is the only PKC isoform recruited to the immunological synapse after T cell receptor stimulation, suggesting that its activation mechanism differs from that of the other isoforms. Previous studies have suggested that this selective PKC recruitment may operate via a Vav-regulated, cytoskeletal-dependent mechanism, independent of the classical phospholipase C/diacylglycerol pathway. Here, we demonstrate that, together with tyrosine phosphorylation of PKC in the regulatory domain, binding of phospholipase C-dependent diacylglycerol is required for PKC recruitment to the T cell synapse. In addition, we demonstrate that diacylglycerol kinase alpha-dependent diacylglycerol phosphorylation provides the negative signal required for PKC inactivation, ensuring fine control of the T cell activation response.
Díaz-Flores
Ernesto
E
Department of Immunology and Oncology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Cantoblanco, E-28049 Madrid, Spain.
Siliceo
María
M
Martínez-A
Carlos
C
Mérida
Isabel
I
D002462:Cell Membrane / Q000201:enzymology*; D019852:Diacylglycerol Kinase / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D051966:Phospholipase C gamma; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D000074121:Protein Kinase C-theta; D043643:Receptor, Muscarinic M1; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D011976:Receptors, Muscarinic / Q000235:genetics; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection; D010738:Type C Phospholipases / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
D004075:Diglycerides; D007527:Isoenzymes; D043643:Receptor, Muscarinic M1; D011948:Receptors, Antigen, T-Cell; D011976:Receptors, Muscarinic; D014443:Tyrosine; D019852:Diacylglycerol Kinase; C076233:PRKCQ protein, human; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta; D010738:Type C Phospholipases; D051966:Phospholipase C gamma