CD28 signals through acidic sphingomyelinase.
T cell receptor recognition of antigen can lead either to T lymphocyte differentiation and proliferation or to a state of unresponsiveness, which is dependent on whether appropriate costimulatory signals are provided to the mature T cell. We have investigated a novel intracellular signaling pathway provided by the costimulatory molecule CD28. CD28 engagement triggers the activation of an acidic sphingomyelinase (A-SMase), which results in the generation of ceramide, an important lipid messenger intermediate. A-SMase activation by CD28 occurred in resting as well as in activated primary T cells or leukemic Jurkat cells. In contrast, ligation of either CD3 or CD2 did not result in A-SMase activation. Overexpression of recombinant A-SMase in Jurkat T cells substituted for CD28 with regard to nuclear factor-kB activation. These data suggest that CD28 provides an important costimulatory signal by activation of an acidic sphingomyelinase pathway.
Boucher
L M
LM
Institute of Medical Microbiology, Technical University of Munich, Germany.
Wiegmann
K
K
Fütterer
A
A
Pfeffer
K
K
Machleidt
T
T
Schütze
S
S
Mak
T W
TW
Krönke
M
M
D000818:Animals; D018106:CD28 Antigens / Q000502:physiology*; D002454:Cell Differentiation; D002460:Cell Line; D006224:Cricetinae; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D007700:Kinetics; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010835:Phytohemagglutinins; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015398:Signal Transduction; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000502:physiology*
D018106:CD28 Antigens; D010835:Phytohemagglutinins; D011948:Receptors, Antigen, T-Cell; D013108:Sphingomyelin Phosphodiesterase