title: CD43 regulates the threshold for T cell activation by targeting Cbl functions.
abstract: T cell (TC) activation requires the coordinated signaling of the T cell receptor (TCR) and coreceptor molecules, allowing TCs to respond to lower degrees of TCR occupancy. Coreceptor molecules set the threshold for TC activation by controlling different regulatory signaling loops. The Cbl family members prevent undesired activation of T cells by regulating TCR signals. In this report, we show that TC prestimulation by the CD43 coreceptor molecule before TCR engagement inhibits TCR-dependent c-Cbl tyrosine phosphorylation, c-Cbl interaction with the adapter molecule Crk-L and promotes Cbl-b degradation in a PKCθ-dependent manner. Consequently, the prolonged tyrosine phosphorylation and delayed degradation of ZAP-70 and of the ζ chain lead to enhanced mitogen-activated protein kinase activation and robust TC response. These data indicates that CD43-mediated signals lower the threshold for TC activation by restricting the c-Cbl and Cbl-b inhibitory effects on TCR signaling. In addition to the strength and duration of intracellular signals, our data underscore temporality with which certain molecules are engaged as yet another mechanism to fine tune TC signal quality, and ultimately immune function.
authors: Instituto de Biotecnología, Departamento de Medicina Molecular y Bioprocesos, Universidad Nacional Autónoma de México, Cuernavaca, Mor. México 62210.
authors: Gustavo
authors: G
authors: Pedraza-Alva
authors: Lilia B
authors: LB
authors: Mérida
authors: Roxana
authors: R
authors: del Rio
authors: Nora A
authors: NA
authors: Fierro
authors: Mario E
authors: ME
authors: Cruz-Muñoz
authors: Norma
authors: N
authors: Olivares
authors: Erika
authors: E
authors: Melchy
authors: Vivian
authors: V
authors: Igras
authors: Georg A
authors: GA
authors: Holländer
authors: Steven J
authors: SJ
authors: Burakoff
authors: Yvonne
authors: Y
authors: Rosenstein
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D019169:Jurkat Cells; D051917:Leukosialin / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology / Q000502:physiology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D050721:Proto-Oncogene Proteins c-cbl / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*
chemical_list: D051917:Leukosialin; D011948:Receptors, Antigen, T-Cell; C465014:SPN protein, human; D050721:Proto-Oncogene Proteins c-cbl; D020928:Mitogen-Activated Protein Kinases; C067419:CBL protein, human