TPO is a key regulator of megakaryocytopoiesis and thrombopoiesis. TPO binds to its receptor, the cellular homologue of the myeloproliferative leukemia virus oncogene (c-Mpl), and stimulates the proliferation and maturation of megakaryocytes. MPL does not possess kinase activity, thus the receptor associates with intracytoplasmic tyrosine kinases, janus kinase 2 (JAK2), for signal transduction. ?JAK2 is also important for MPL stability and cell-surface expression. TPO is able to promote the survival, self-renewal, and expansion of hematopoietic stem cells and primitive multi-lineage progenitor cells. TPO levels in blood and bone marrow are inversely related to platelet count. ?The regulation of TPO levels is mediated by its receptor c-Mpl (uptake and destruction). TPO is upregulated by PDGF and FGF-2, and it is downregulated by PF4, thrombospondin, and TGF-β in bone marrow stromal cells. In hepatocytes, HGF enhances TPO mRNA expression. During acute-phase response, IL-6 induces TPO transcription in the liver. Elevated plasma TPO levels exist in several hematological diseases associated with thrombocytopenia, coronary syndromes, and sepsis. Besides its hematopoietic effects, TPO is expressed in the brain where it promotes apoptosis of hypoxia sensitized neurons and inhibits neuronal differentiation by blocking NGF-induced signaling. Increased TPO concentrations are present in the cerebrospinal fluid of some patients with bacterial or viral meningitis.
Size
10 μg
Concentration
n/a
Applications
BA
Other Names
Megakaryocyte Colony Stimulating Factor (MKCSF), Myeloproliferative leukemia virus oncogene ligand (Mpl-ligand), Megakaryocyte growth and development factor (MGDF), THPO