Tec protein tyrosine kinase inhibits CD25 expression in human T-lymphocyte.
The Tec protein tyrosine kinase (PTK) belongs to a group of structurally related nonreceptor PTKs that also includes Btk, Itk, Rlk, and Bmx. Previous studies have suggested that these kinases play important roles in hematopoiesis and in the lymphocyte signaling pathway. Despite evidence suggesting the involvement of Tec in the T-lymphocyte activation pathway via T-cell receptor (TCR) and CD28, Tec's role in T-lymphocytes remains unclear because of the lack of apparent defects in T-lymphocyte function in Tec-deficient mice. In this study, we investigated the role of Tec in human T-lymphocyte using the Jurkat T-lymphoid cell line stably transfected with a cDNA encoding Tec. We found that the expression of wild-type Tec inhibited the expression of CD25 induced by TCR cross-linking. Second, we observed that LFM-A13, a selective inhibitor of Tec family PTK, rescued the suppression of TCR-induced CD25 expression observed in wild-type Tec-expressing Jurkat cells. In addition, expression of kinase-deleted Tec did not alter the expression level of CD25 after TCR ligation. We conclude that Tec PTK mediates signals that negatively regulate CD25 expression induced by TCR cross-linking. This, in turn, implies that this PTK plays a role in the attenuation of IL-2 activity in human T-lymphocytes.
Susaki
Kentaro
K
Division of Endocrinology and Metabolism, Hematology, Rheumatology, and Respiratory Medicine, Department of Internal Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
Kitanaka
Akira
A
Dobashi
Hiroaki
H
Kubota
Yoshitsugu
Y
Kittaka
Katsuharu
K
Kameda
Tomohiro
T
Yamaoka
Genji
G
Mano
Hiroyuki
H
Mihara
Keichiro
K
Ishida
Toshihiko
T
D000577:Amides / Q000494:pharmacology; D000911:Antibodies, Monoclonal; D017252:CD3 Complex / Q000276:immunology; D003001:Cloning, Molecular; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics; D009570:Nitriles / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism*; D017384:Sequence Deletion; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D014162:Transfection
D000577:Amides; D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; C118451:LFM A13; D009570:Nitriles; D011948:Receptors, Antigen, T-Cell; C089848:Tec protein-tyrosine kinase; D011505:Protein-Tyrosine Kinases