Thrombopoietin
Glycoprotein hormone that stimulates megakaryocyte proliferation and platelet production through the c-Mpl receptor.
Chemical Identity
| Property | Value |
|---|---|
| Molecular Weight | ~65-85 kDa (glycosylated) |
| Gene | THPO (MPL ligand) |
| Amino Acids | 332 (full length), 353 (precursor) |
| Glycosylation | N-linked and O-linked |
| Receptor | c-Mpl (TPO receptor) |
Structure
Thrombopoietin (TPO) is a glycoprotein hormone with an EPO-like N-terminal domain (first 153 amino acids) responsible for receptor binding and a heavily glycosylated C-terminal domain that stabilizes the protein in circulation. The C-terminal domain has no sequence homology with other cytokines.
Mechanism of Action
TPO binds c-Mpl receptors on hematopoietic stem cells, megakaryocyte progenitors, and mature megakaryocytes, activating JAK2/STAT5 and MAPK pathways. This promotes stem cell survival, megakaryocyte proliferation, endomitosis (polyploidization), and proplatelet formation. TPO is the primary regulator of platelet production.
Clinical Applications
- Platelet homeostasis: Primary regulator of platelet count
- ITP: TPO levels inappropriately normal (target for therapy)
- Chemotherapy thrombocytopenia: Recombinant TPO tested in trials
- Stem cell mobilization: Synergy with G-CSF
- Recombinant forms: Romiplostim (peptibody), eltrombopag (small molecule)
Pharmacology
- Half-life: 20-40 hours (endogenous)
- Regulation: Platelet and megakaryocyte mass controls TPO clearance
- Production: Liver (primary), kidney, bone marrow
- Stem cells: Acts on most primitive hematopoietic cells
References
- Kaushansky, K., et al. (1994). Cloning of the ligand for the c-Mpl receptor. Nature, 369, 568-571.
- Kuter, D.J. (2013). The biology of thrombopoietin and thrombopoietin receptor agonists. International Journal of Hematology, 98, 10-23.
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