Structural requirements for CD28-mediated costimulation of IL-2 production in Jurkat T cells.
Although under certain conditions an association with phosphatidylinositol 3'-kinase (PI3-K) appears to be critical for CD28 signaling, mutation of the PI3-K binding site (Tyr 170) does not alter the costimulatory ability of murine CD28 (mCD28) in Jurkat T cells. To define the structural requirements for this PI3-K-independent signaling, we expressed a series of mCD28 mutants in Jurkat. Mutation to Phe of all four cytoplasmic Tyr residues together (ALL F mutant) greatly reduced the ability of mCD28 to augment IL-2 production. Isolated re-constitution of Tyr 188, but not 170, 185, or 197, restored the ability of ALL F mCD28 to deliver a costimulus. Thus, a signal based upon Tyr 188 can deliver a costimulus for the enhancement of IL-2 production by Jurkat cells.
Truitt
K E
KE
Department of Medicine, San Francisco General Hospital, and the University of California, San Francisco, CA 94143, USA.
Nagel
T
T
Suen
L F
LF
Imboden
J B
JB
D000595:Amino Acid Sequence; D018106:CD28 Antigens / Q000502:physiology*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000502:physiology; D019000:Phosphotyrosine / Q000737:chemistry; D017354:Point Mutation; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000502:physiology*; D014407:Tumor Cells, Cultured
D018106:CD28 Antigens; D007376:Interleukin-2; D019000:Phosphotyrosine; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor)