Expression and activation of the nonreceptor tyrosine kinase Tec in human B cells.
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.
Kitanaka
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Department of Hematology-Oncology, St Jude Children's Research Hospital, Lauderdale, Memphis, TN 38105, USA.
Mano
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Conley
M E
ME
Campana
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D
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000361:Agammaglobulinemia / Q000235:genetics / Q000473:pathology; D015703:Antigens, CD; D018941:Antigens, CD19 / Q000378:metabolism; D000943:Antigens, Differentiation / Q000378:metabolism; D001402:B-Lymphocytes / Q000201:enzymology*; D002460:Cell Line; D002461:Cell Line, Transformed; D004789:Enzyme Activation; D008040:Genetic Linkage; D004854:Herpesvirus 4, Human; D006801:Humans; D008562:Membrane Glycoproteins; D009244:NAD+ Nucleosidase / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D014960:X Chromosome
D015703:Antigens, CD; D018941:Antigens, CD19; D000943:Antigens, Differentiation; D008562:Membrane Glycoproteins; D011947:Receptors, Antigen, B-Cell; C089848:Tec protein-tyrosine kinase; D011505:Protein-Tyrosine Kinases; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1