Fas-activated serine/threonine kinase (FAST) phosphorylates TIA-1 during Fas-mediated apoptosis.
We have identified a serine/threonine kinase that is rapidly activated during Fas-mediated apoptosis. Fas-activated serine/threonine kinase (FAST) is phosphorylated on serine and threonine residues in Jurkat cells. In response to Fas ligation, it is rapidly dephosphorylated and concomitantly activated to phosphorylate TIA-1, a nuclear RNA-binding protein that has been implicated as an effector of apoptosis. Phosphorylation of TIA-1 precedes the onset of DNA fragmentation, suggesting a role in signaling downstream events in the apoptotic program. Our results introduce Fast and TIA-1 as components of a molecular cascade involved in signaling Fas-mediated apoptosis.
Tian
Q
Q
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Taupin
J
J
Elledge
S
S
Robertson
M
M
Anderson
P
P
D000595:Amino Acid Sequence; D000954:Antigens, Surface / Q000502:physiology*; D017209:Apoptosis / Q000502:physiology*; D016384:Consensus Sequence; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D010766:Phosphorylation; D039102:Poly(A)-Binding Proteins; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000302:isolation & purification / Q000378:metabolism*; D011506:Proteins; D016601:RNA-Binding Proteins / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D000074019:T-Cell Intracellular Antigen-1; D014407:Tumor Cells, Cultured; D019014:fas Receptor
D000954:Antigens, Surface; D018076:DNA, Complementary; D008565:Membrane Proteins; D039102:Poly(A)-Binding Proteins; D011506:Proteins; D016601:RNA-Binding Proteins; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human; D019014:fas Receptor; C095367:FASTK protein, human; D017346:Protein Serine-Threonine Kinases