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Expression and Activation of the Nonreceptor Tyrosine Kinase Tec
in Human B Cells
Akira Kitanaka,
Hiroyuki Mano,
Mary Ellen Conley, and
Dario Campana
From the Departments of Hematology-Oncology and Immunology, St Jude
Children's Research Hospital and University of Tennessee College of
Medicine, Memphis TN; and the Department of Molecular Biology, Jichi
Medical School, Tochigi, Japan.
The tyrosine kinase Tec belongs to a new group of structurally
related nonreceptor tyrosine kinases that also includes Btk and Itk.
Previous studies have suggested that these kinases have lineage-specific roles, with Tec being involved mainly in the regulation of cytokine-mediated myeloid cell growth and
differentiation. In this study, we investigated expression and
activation of Tec in human B-lymphoid cell lines representing different
stages of B-cell maturation, including pro-B (RS4;11, 380, REH), pre-B
(NALM6), and mature B (Ramos, and one Epstein-Barr virus
[EBV]-transformed lymphoblastoid line) cells. Like Btk, Tec protein
was expressed in all B-cell lines tested. Tec was also highly expressed
in two EBV-transformed lymphoblastoid lines derived from patients with X-linked agammaglobulinemia (XLA) lacking Btk expression, as well as in
tonsillar lymphoid cells. In surface immunoglobulin-positive B cells
(Ramos), ligation of the B-cell antigen receptor (BCR) with anti-IgM
antibodies caused marked tyrosine phosphorylation of Tec and increased
Tec tyrosine kinase activity. Likewise, cross-linking of CD19 with a
monoclonal antibody in BCR-negative pro-B (RS4;11, 380) and pre-B
(NALM6) cells induced Tec tyrosine phosphorylation and increased Tec
autophosphorylation, as well as Btk activation. Tyrosine
phosphorylation of Tec, but not of Btk, was detectable in RS4;11 cells
after CD38 ligation, suggesting that these kinases are regulated
differently. We conclude that Tec is expressed and can be stimulated
throughout human B-cell differentiation, implying that this tyrosine
kinase plays a role in B-cell development and activation.
Blood, Vol. 91 No. 3 (February 1), 1998:
pp. 940-948
© 1998 by The American Society of Hematology.
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