What is the function of thrombopoietin?

Thrombopoietin is a glycoprotein hormone produced by the liver and kidney which regulates the production of platelets. It stimulates the production and differentiation of megakaryocytes, the bone marrow cells that bud off large numbers of platelets.

Is thrombopoietin a cytokine?

The cytokine thrombopoietin (TPO) is the chief regulator of megakaryocyte (MK) and platelet production, signaling via its receptor, MPL (TPO-R). The receptor was first identified in 1992 (1) and its ligand, TPO, was cloned not long after by several independent groups (2–7).

How is TPO regulated?

A steady-state amount of hepatic thrombopoietin (TPO) is regulated by platelet c-Mpl receptor–mediated uptake and destruction of the hormone. Hepatic production of the hormone is depicted. Upon binding to platelet c-Mpl receptors, the hormone is removed from the circulation and destroyed, which reduces blood levels.

What is Thrombopoiesis?

Thrombopoiesis is the formation of platelets in the Bone marrow. Thrombopoietin is the main regulator of thrombopoiesis. Thrombopoietin affects most aspects of the production of platelets.

What controls platelet production?

Platelets are produced in the bone marrow, the same as the red cells and most of the white blood cells. Platelets are produced from very large bone marrow cells called megakaryocytes. The dominant hormone controlling megakaryocyte development is thrombopoietin (often abbreviated as TPO).

What is a megakaryocyte?

Megakaryocytes are cells in the bone marrow responsible for making platelets, which are necessary for blood clotting. Yale researchers have discovered how megakaryocytes — giant blood cells that produce wound-healing platelets — manage to grow 10 to 15 times larger than other blood cells.

What hormone controls Thrombopoiesis?

Megakaryocytes are produced from stem cells in the bone marrow by a process called thrombopoiesis. Megaryocytes create platelets by releasing protoplatelets that break up into numerous smaller, functional platelets. Thrombopoiesis is stimulated and regulated by the hormone thrombopoietin.

What does Thrombopoiesis produce?

Thrombopoiesis—from thrombos (Gr., clot)—refers to the production of platelets, which are small (2 to 4 µm), round to ovoid, anucleate cells within blood vessels.

Where does thrombopoietin and MPL signaling take place?

The hematopoietic cytokine thrombopoietin (Thpo) signals through its receptor Mpl, which is expressed on megakaryocytes/platelets and hematopoietic stem cells (HSC), and mediates megakaryopoiesis and HSC maintenance.

How does thrombopoietin bind to the TPO-R receptor?

Thrombopoietin acts by binding to the extracellular portion of partially predimerized cell surface TPO-R, thought to cause a change in the receptor dimer arrangement and/or monomer–dimer equilibrium, which initiates a cascade of signaling events within the target cell.

What is the role of thrombopoietin in neoplasms?

This pathologic TPO-R activation is associated with a large fraction of human myeloproliferative neoplasms. The cytokine thrombopoietin (TPO) is the chief regulator of megakaryocyte (MK) and platelet production, signaling via its receptor, MPL (TPO-R).

Are there disease causing mutations in the thrombopoietin receptor?

The identification of disease-causing mutations in the receptor has, however, offered some insight into structure and function relationships, as has artificial means of receptor activation, through TPO mimetics, transmembrane-targeting receptor agonists, and engineering in dimerization domains.