Cross-linking of CD26 by antibody induces tyrosine phosphorylation and activation of mitogen-activated protein kinase.
CD26, a T-cell activation antigen that has dipeptidyl peptidase IV activity in its extracellular domain and has also been shown to play an important role in T-cell activation. The earliest biochemical events seen in stimulated T lymphocytes activated through the engagement of the T-cell receptor (TCR) is the tyrosine phosphorylation of a panel of cellular proteins. In this study we demonstrate that antibody-induced cross-linking of CD26-in CD26-transfected Jurkat cells induced tyrosine phosphorylation of several intracellular proteins with a similar pattern to that seen after TCR/CD3 stimulation. Herbimycin A, an inhibitor of the src family protein tyrosine kinases dramatically inhibited this CD26-mediated effect on tyrosine phosphorylation. Major tyrosine phosphorylated proteins were identified by immunoblotting, and included p56lck, p59fyn, zeta associated protein-tyrosine kinase of 70,000 MW (ZAP-70), mitogen-activated protein (MAP) kinase, c-Cb1, and phospholipase C gamma. CD26-induced tyrosine phosphorylation of MAP kinase correlated with increased MAP kinase activity. In addition, CD26 was costimulatory to CD3 signal transduction since co-cross-linking of CD26 and CD3 antigens induced prolonged and increased tyrosine phosphorylation in comparison with CD3 activation alone. We therefore conclude that CD26 is a true costimulatory entity that can up-regulate the signal transducing properties of the TCR.
Hegen
M
M
Division of Tumor Immunology, DanaFarber Cancer Institute, Boston, MA 02115, USA.
Kameoka
J
J
Dong
R P
RP
Schlossman
S F
SF
Morimoto
C
C
D000911:Antibodies, Monoclonal / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D018819:Dipeptidyl Peptidase 4 / Q000276:immunology*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D015151:Immunoblotting; D008213:Lymphocyte Activation / Q000502:physiology*; D008934:Mitogens / Q000276:immunology; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000502:physiology*
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D008934:Mitogens; D014443:Tyrosine; D011494:Protein Kinases; D018819:Dipeptidyl Peptidase 4