TEC PROTEIN-TYROSINE KINASE IS INVOLVED IN THE THROMBOPOIETIN C-MPL SIGNALING PATHWAY/

Thrombopoietin (TPO) is the ligand of the proto-oncogene product, c-Mp l, and supports the growth and maturation of megakaryocytic cells. Alt hough much attention has been paid to the in vivo role of the TPO/c-Mp l system in the context of maintenance of circulating platelets, still little is understood about how activation of c-Mpl leads to mitogenes is and differentiation inside cells. Tec protein-tyrosine kinase (MX) is the prototype of a recently emerging subfamily of nonreceptor type PTKs. Tec has been demonstrated to be activated by a wide range of cyt okine stimulations. In this paper we show that TPO stimulation also ra pidly enhances tyrosine-phosphorylation and activity of the Tec kinase in a human TPO-dependent cell line. In addition, the Vav protein, a b lood cell-specific signaling molecule, is shown to be tyrosine-phospho rylated in response to TPO and to be constitutively associated with th e Tec protein. From this evidence, we conclude that Tec is involved in the intracellular signaling system of TPO/c-Mpl.