CD38 ligation results in activation of the Raf-1/mitogen-activated protein kinase and the CD3-zeta/zeta-associated protein-70 signaling pathways in Jurkat T lymphocytes.
CD38 ligation with the specific mAb IB4 induced early and late signaling events in Jurkat T cells, as judged by the transient induction of tyrosine phosphorylation of phospholipase C-gamma1, c-Cbl, zeta-associated protein (ZAP)-70, Shc, extracellular signal-regulated protein kinase-2 (Erk-2) as mitogen-activated protein (MAP) kinase, and increased expression of the activation Ag CD69. In addition, CD38 ligation induced Ras-dependent events such as Erk-2 mobility shift and increased Erk-2 kinase activity. Further evidence that Erk-2 activation is regulated by CD38 ligation was obtained indirectly with the observed induction of Raf-1, Lck, and Sos-1 mobility shifts, processes that are believed to be dependent, at least in part, on MAP kinase activation. Using a protein tyrosine kinase inhibitor, herbimycin A, or a protein kinase C inhibitor, Ro-31-8220, we found that the anti-CD38-induced Erk-2 activation is both protein tyrosine kinase and protein kinase C dependent. CD38 ligation also resulted in increased CD3-zeta tyrosine phosphorylation and its association with ZAP-70. CD38 ligation in a Jurkat Lck-deficient mutant, JCam1, failed to induce substrate tyrosine phosphorylation and activation of Erk-2. These data indicated that in Jurkat T cells, CD38 receptor triggering results in Lck-regulated activation of both Raf-1/MAP kinase and CD3-zeta/ZAP-70/phospholipase C-gamma1 signaling pathways.
Zubiaur
M
M
Department of Cellular Biology and Immunology, Instituto de Parasitología y Biomedicina, Consejo Superior de Investigaciones Científicas (CSIC), Granada, Spain.
Izquierdo
M
M
Terhorst
C
C
Malavasi
F
F
Sancho
J
J
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology / Q000378:metabolism*; D016227:Benzoquinones; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D019169:Jurkat Cells; D047029:Lactams, Macrocyclic; D008024:Ligands; D008562:Membrane Glycoproteins; D009699:N-Glycosyl Hydrolases / Q000276:immunology / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf; D011809:Quinones / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D051746:ZAP-70 Protein-Tyrosine Kinase
D015703:Antigens, CD; D000943:Antigens, Differentiation; D016227:Benzoquinones; D004791:Enzyme Inhibitors; D007211:Indoles; D047029:Lactams, Macrocyclic; D008024:Ligands; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D011809:Quinones; D017828:Rifabutin; C020754:herbimycin; D011505:Protein-Tyrosine Kinases; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D009699:N-Glycosyl Hydrolases; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1; C064758:Ro 31-8220