Costimulatory signals for human T-cell activation induce nuclear translocation of pp19/cofilin.
Resting T lymphocytes that have recognized antigen bound to a major histocompatibility complex molecule with the T-cell receptor require costimulatory signals through accessory receptors, including CD2, CD4, CD8, and CD28, for their clonal growth and expression of their functional repertoires. Absence of costimulation, in contrast, can induce clonal anergy in vitro and selective tolerance in vivo. Here we have defined a potential intracellular messenger for T-cell activation which is strictly regulated by costimulatory signals mediated through accessory receptors: pp19/cofilin, a small actin-binding protein, undergoes dephosphorylation and subsequent translocation from the cytosol into the nucleus. In untransformed T cells this process correlates with functional responses essential for the induction of T-cell proliferation (i.e., production of interleukin 2). Moreover, spontaneous dephosphorylation as well as nuclear translocation of pp19/cofilin occur in the autonomously proliferating T-lymphoma cell line Jurkat.
Samstag
Y
Y
German Cancer Research Center, Heidelberg.
Eckerskorn
C
C
Wesselborg
S
S
Henning
S
S
Wallich
R
R
Meuer
S C
SC
D051339:Actin Depolymerizing Factors; D000595:Amino Acid Sequence; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D002999:Clone Cells; D006801:Humans; D008213:Lymphocyte Activation; D016399:Lymphoma, T-Cell; D008840:Microfilament Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D010449:Peptide Mapping; D010710:Phosphates / Q000378:metabolism; D010761:Phosphorus Radioisotopes; D010766:Phosphorylation; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D051339:Actin Depolymerizing Factors; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D010710:Phosphates; D010761:Phosphorus Radioisotopes