Tec protein-tyrosine kinase is an effector molecule of Lyn protein-tyrosine kinase.
The Tec family is a recently emerging subfamily among nonreceptor type protein-tyrosine kinases (PTKs) consisting of Tec, Txk, Btk, Bmx, and Itk/Tsk/Emt. They have a long amino-terminal unique region containing a pleckstrin homology domain and a Tec-homology domain. We could previously show that, through the Tec-homology domain, Tec is bound to Lyn kinase both in vitro and in vivo. Because Tec is coexpressed with Lyn in many hematopoietic cell types, it has been intriguing to investigate the biological role of the Tec-Lyn association. Here we demonstrate that Lyn can phosphorylate tyrosine residues of the Tec protein, and thereby activate Tec in 3T3 fibroblasts. However, coexpression of Tec has little effect on the phospho-tyrosine-contents of Lyn. By using the in vitro kinase assay and the yeast system, we could prove that the Tec protein is a direct substrate of the Lyn kinase both in vitro and in vivo. From this evidence we conclude that Tec acts downstream of Lyn in intracellular signaling pathways. This is a novel case where one PTK is phosphorylated and regulated by another.
Mano
H
H
Department of Molecular Biology, Jichi Medical School, Tochigi-ken, Japan.
Yamashita
Y
Y
Miyazato
A
A
Miura
Y
Y
Ozawa
K
K
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D004789:Enzyme Activation; D015870:Gene Expression; D007163:Immunosorbent Techniques; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D014162:Transfection; D019061:src-Family Kinases / Q000737:chemistry / Q000235:genetics
D019000:Phosphotyrosine; C089848:Tec protein-tyrosine kinase; D011505:Protein-Tyrosine Kinases; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases