Details

Autor(en) / Beteiligte

• Hercus, Timothy R.
• Thomas, Daniel
• Guthridge, Mark A.
• Ekert, Paul G.
• King-Scott, Jack
• Parker, Michael W.
• Lopez, Angel F.

Titel

The granulocyte-macrophage colony-stimulating factor receptor: linking its structure to cell signaling and its role in disease

Ist Teil von

• Blood, 2009-08, Vol.114 (7), p.1289-1298

Ort / Verlag

Washington, DC: Elsevier Inc

Erscheinungsjahr

2009

Link zum Volltext

Quelle

Elektronische Zeitschriftenbibliothek - Freely accessible e-journals

Beschreibungen/Notizen

• Already 20 years have passed since the cloning of the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor α-chain, the first member of the GM-CSF/interleukin (IL)–3/IL-5 family of hemopoietic cytokine receptors to be molecularly characterized. The intervening 2 decades have uncovered a plethora of biologic functions transduced by the GM-CSF receptor (pleiotropy) and revealed distinct signaling networks that couple the receptor to biologic outcomes. Unlike other hemopoietin receptors, the GM-CSF receptor has a significant nonredundant role in myeloid hematologic malignancies, macrophage-mediated acute and chronic inflammation, pulmonary homeostasis, and allergic disease. The molecular mechanisms underlying GM-CSF receptor activation have recently been revealed by the crystal structure of the GM-CSF receptor complexed to GM-CSF, which shows an unexpected higher order assembly. Emerging evidence also suggests the existence of intracellular signosomes that are recruited in a concentration-dependent fashion to selectively control cell survival, proliferation, and differentiation by GM-CSF. These findings begin to unravel the mystery of cytokine receptor pleiotropy and are likely to also apply to the related IL-3 and IL-5 receptors as well as other heterodimeric cytokine receptors. The new insights in GM-CSF receptor activation have clinical significance as the structural and signaling nuances can be harnessed for the development of new treatments for malignant and inflammatory diseases.