title: TCR-induced sumoylation of the kinase PKC-θ controls T cell synapse organization and T cell activation.
abstract: Sumoylation regulates many cellular processes, but its role in signaling via the T cell antigen receptor (TCR) remains unknown. We found that the kinase PKC-θ was sumoylated upon costimulation with antigen or via the TCR plus the coreceptor CD28, with Lys325 and Lys506 being the main sumoylation sites. We identified the SUMO E3 ligase PIASxβ as a ligase for PKC-θ. Analysis of primary mouse and human T cells revealed that sumoylation of PKC-θ was essential for T cell activation. Desumoylation did not affect the catalytic activity of PKC-θ but inhibited the association of CD28 with PKC-θ and filamin A and impaired the assembly of a mature immunological synapse and central co-accumulation of PKC-θ and CD28. Our findings demonstrate that sumoylation controls TCR-proximal signaling and that sumoylation of PKC-θ is essential for the formation of a mature immunological synapse and T cell activation.
authors.affiliation: State Key Laboratory of Biocontrol, Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xu-Dong
authors.initials: XD
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Biocontrol, Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Gong
authors.affiliation: State Key Laboratory of Biocontrol, Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Zhi-Long
authors.initials: ZL
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Biocontrol, Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Bei-Ni
authors.initials: BN
authors.lastname: Gong
authors.affiliation: State Key Laboratory of Biocontrol, Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.|Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
authors.forename: Ji-Ji
authors.initials: JJ
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, China.
authors.forename: Chuan-Qi
authors.initials: CQ
authors.lastname: Zhong
authors.affiliation: State Key Laboratory of Biocontrol, Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Qi-Long
authors.initials: QL
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Biocontrol, Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Liang-Hui
authors.initials: LH
authors.lastname: Diao
authors.affiliation: State Key Laboratory of Biocontrol, Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Anlong
authors.initials: A
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, China.
authors.forename: Jiahuai
authors.initials: J
authors.lastname: Han
authors.affiliation: Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
authors.forename: Amnon
authors.initials: A
authors.lastname: Altman
authors.affiliation: State Key Laboratory of Biocontrol, Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yingqiu
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D001665:Binding Sites; D018106:CD28 Antigens / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D064448:Filamins / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D054992:Immunological Synapses / Q000378:metabolism; D007527:Isoenzymes / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D008239:Lysine / Q000737:chemistry; D051379:Mice; D018345:Mice, Knockout; D016297:Mutagenesis, Site-Directed; D050828:Protein Inhibitors of Activated STAT / Q000378:metabolism; D011493:Protein Kinase C / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000074121:Protein Kinase C-theta; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction; D058207:Sumoylation; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology* / Q000276:immunology*; D018418:Th2 Cells / Q000166:cytology / Q000201:enzymology / Q000276:immunology
chemical_list: D018106:CD28 Antigens; D064448:Filamins; D007527:Isoenzymes; C501001:PIAS2 protein, human; D050828:Protein Inhibitors of Activated STAT; D011948:Receptors, Antigen, T-Cell; C076233:PRKCQ protein, human; C489593:Prkcq protein, mouse; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta; D008239:Lysine