The Hsp90-specific inhibitor, geldanamycin, blocks CD28-mediated activation of human T lymphocytes.
The 90 kDa heat shock protein (Hsp90) is a molecular chaperone aiding the folding of nuclear hormone receptors and protein kinases. Hsp90-mediated folding can be disrupted by the Hsp90-specific drug, geldanamycin. Here we provide evidence for the inhibition of the CD28-specific BW 828 antibody-mediated activation of human T lymphocyte proliferation, IL-2 secretion and IL-2 receptor expression by geldanamycin. Our results suggest that the major cytoplasmic chaperone, Hsp90, plays an important role in CD28-mediated T lymphocyte activation.
Schnaider
T
T
Department of Medical Chemistry, Semmelweis University, Budapest, Hungary.
Somogyi
J
J
Csermely
P
P
Szamel
M
M
D019138:Antibodies, Blocking / Q000494:pharmacology; D016227:Benzoquinones; D018106:CD28 Antigens / Q000276:immunology / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D047029:Lactams, Macrocyclic; D008213:Lymphocyte Activation / Q000187:drug effects; D011809:Quinones / Q000494:pharmacology*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*
D019138:Antibodies, Blocking; D016227:Benzoquinones; D018106:CD28 Antigens; D004791:Enzyme Inhibitors; D018841:HSP90 Heat-Shock Proteins; D007376:Interleukin-2; D047029:Lactams, Macrocyclic; D011809:Quinones; D015375:Receptors, Interleukin-2; C001277:geldanamycin