Tec protein-tyrosine kinase directly associates with Lyn protein-tyrosine kinase through its N-terminal unique domain.
Most of non-receptor-type protein-tyrosine kinases share common structures, such as N-terminal unique domains, Src homology region (SH)-2 domains, SH-3 domains and kinase domains. Although vast effort has brought some information about the in vivo roles of SH-2, -3 and kinase domains, little is still understood about the function of N-terminal unique domain. By utilizing the glutathione S-transferase (GST)-fusion system, we have investigated the role of N-terminal unique domain of the Tec protein-tyrosine kinase in a mouse IL-3-dependent myeloid cell line. We could reveal that the C-terminal half of the Tec N-terminal unique domain (NTec2 region) can bind to a set of tyrosine-phosphorylated cellular proteins in vitro in an IL-3-dependent manner. Surprisingly, p56/53Lyn constitutively binds to the NTec2 region. Among the NTec2-bound Lyn proteins, only the p56 form seems to be inducibly tyrosine-phosphorylated in response to IL-3. Binding domain of Lyn to the NTec2 region was localized to its SH-3 domain. Tec was also shown to make a stable complex with Lyn in vivo. This is the first report demonstrating the direct association between distinct cytoplasmic protein-tyrosine kinases, especially through N-terminal unique domain.
Mano
H
H
Department of Molecular Biology, Jichi Medical School, Tochigi-ken, Japan.
Sato
K
K
Yazaki
Y
Y
Hirai
H
H
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D015398:Signal Transduction; D014443:Tyrosine; D019061:src-Family Kinases
D014443:Tyrosine; C089848:Tec protein-tyrosine kinase; D011505:Protein-Tyrosine Kinases; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases