Thrombopoietin signal transduction: Studies from cell lines and primary cells

Thrombopoietin (TPO) and its receptor Mpl support all of the developmental step necessary for megakaryocytopoiesis. In the past few years, the signali ng pathways utilized by this member of the cytokine receptor family have be en extensively studied, especially JAK/STAT, Ras/MAP kinase, Shc, and other adapter molecules. Many if not most of the secondary signaling pathways ac tivated by thrombopoietin have also been identified upon binding of other h ematopoietic growth factors to their cognate receptors, making the study of Mpl signaling representative of the field in general. However, identifying unique molecules or combinations of signals that direct megakaryocyte deve lopment has been an elusive goal and has led some investigators to conclude that there is little specificity during Mpl signal transduction. In this a rticle we review the data regarding Mpl signaling with particular attention to the methods employed and critical interpretation of the data generated. Future studies will have to focus on primary bone marrow cells and intact animal models rather than transformed cell lines. Furthermore, it is likely that a comprehensive, integrative analysis of the many pathways activated by ligand binding will be necessary to understand the physiology of cytokin e signaling, (C) 1999 Academic Press.