BACKGROUND Thrombopoietin (TPO) is a novel hematopoietic growth factor and a ligand for the c-mpl proto-oncogene that was originally identified as the cellular homologue of the oncogene v-mpl proto-oncogene. The c-mpl proto-oncogene is expressed in hematopoietic tissues, particularly in CD34+ hematopoietic progenitor cells, megakaryocytes, and platelets, whereas its ligand TPO is detected primarily in the liver, kidney, and smooth muscle, with lesser amounts present in the spleen and bone marrow.1 It has been shown that daily infusion of TPO into mice or nonhuman primates induces a marked increase in the counts of platelets, megakaryocytes, and megakaryocytic progenitor cells. Furthermore, c-Mpl- or TPO-deficient mice generated by gene targeting have been demonstrated to exhibit a striking decrease in the number of platelets and megakaryocytic progenitor cells. Interestingly, in the absence of Tpo or c-mpl, the residual megakaryocytes and platelets are morphologically and functionally normal.Therefore, Tpo/mpl is important for controlling megakaryocyte numbers by promoting their survival and/or proliferation as well as differentiation, but is not essential for megakaryocyte cytoplasmic maturation or platelet formation.2
c-Mpl belongs to the type I cytokine receptor family. Ligand binding induces activation of the JAK2 that is associated with the receptor through Box1 and Box2. Activated JAK2 phosphorylates tyrosine residues on cytokine receptors, thereby providing docking sites for several Src homology 2 (SH2) domain–containing downstream signaling proteins. Mpl activates many signaling pathways in hematopoietic cell lines and primary megakaryocytes and platelets, including STAT3 and 5, Shc–Ras–mitogen-activated protein kinase (MAPK), and SHP2–Gab–phosphoinositide-3 kinase–Akt pathways. On the other hand, Lnk, an adptor protein, negatively regulates thrombopoietin (TPO) signaling in megakaryocytes and erythropoietin signaling in erythroblasts. Thus, it is suggested that a balance in positive and negative signals downstream from the TPO signal plays a role in the regulation of the probability of self-renewal in hematopoietic stem cells. These signaling molecules have important roles in hematopoiesis, and dysregulation of these signaling pathways is implicated in leukemogenesis.3
1. Kaushansky, K. & Drachman, J. G.: Oncogen 21:3359-67, 2002
2. Matsumura, I. et al: Mol. Cell. Biol.17:2933-43, 1997
3. Seita, J. et al: Proc. Natl. Acad. Sci. USA 104:2349-54, 2007
Products are for research use only. They are not intended for human, animal, or diagnostic applications.
Target Protein Species:
31.2pg/ml – 2000pg/ml
No detectable cross-reactivity with any other cytokine.
Store at 4°C. Use within 6 months.
ELISA Kits are based on standard sandwich enzyme-linked immunosorbent assay technology. Freshly prepared standards, samples, and solutions are recommended for best results.