Tec protein-tyrosine kinase is involved in the thrombopoietin/c-Mpl signaling pathway.
Thrombopoietin (TPO) is the ligand of the proto-oncogene product, c-Mpl, and supports the growth and maturation of megakaryocytic cells. Although much attention has been paid to the in vivo role of the TPO/c-Mpl system in the context of maintenance of circulating platelets, still little is understood about how activation of c-Mpl leads to mitogenesis and differentiation inside cells. Tec protein-tyrosine kinase (PTK) is the prototype of a recently emerging subfamily of nonreceptor type PTKs. Tec has been demonstrated to be activated by a wide range of cytokine stimulations. In this paper we show that TPO stimulation also rapidly enhances tyrosine-phosphorylation and activity of the Tec kinase in a human TPO-dependent cell line. In addition, the Vav protein, a blood cell-specific signaling molecule, is shown to be tyrosine-phosphorylated in response to TPO and to be constitutively associated with the Tec protein. From this evidence, we conclude that Tec is involved in the intracellular signaling system of TPO/c-Mpl.
Yamashita
Y
Y
Department of Molecular Biology, Jichi Medical School, Tochigi-ken, Japan.
Miyazato
A
A
Shimizu
R
R
Komatsu
N
N
Miura
Y
Y
Ozawa
K
K
Mano
H
H
D018797:Cell Cycle Proteins; D004789:Enzyme Activation; D006801:Humans; D008533:Megakaryocytes / Q000473:pathology; D009363:Neoplasm Proteins; D010750:Phosphoproteins / Q000378:metabolism; D019000:Phosphotyrosine / Q000378:metabolism; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051567:Proto-Oncogene Proteins c-vav; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; D015398:Signal Transduction; D013926:Thrombopoietin / Q000502:physiology*
D018797:Cell Cycle Proteins; C000715470:MAS1 protein, human; D009363:Neoplasm Proteins; D010750:Phosphoproteins; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; C496618:VAV1 protein, human; C082218:MPL protein, human; D019000:Phosphotyrosine; D013926:Thrombopoietin; C089848:Tec protein-tyrosine kinase; D011505:Protein-Tyrosine Kinases