Regulation of myelopoiesis through syntenin-mediated modulation of IL-5 receptor output.

Abstract:

:The granulocyte-macrophage colony-stimulating factor (GM-CSF)/interleukin (IL)-3/IL-5 receptor family regulates the production and function of myeloid cells. These cytokines signal through receptor complexes that consist of unique ligand-binding alpha-chains and common signaling beta-chains. IL-5 is distinct from IL-3 and GM-CSF in its capacity to induce eosinophil development, however, the molecular mechanisms that generate functional diversity within this receptor family are mostly unknown. Here, we characterized the selective IL-5Ralpha-binding adapter protein syntenin in IL-5R function. Syntenin and IL-5Ralpha colocalize at the plasma membrane and in early endosomal compartments. Manipulation of syntenin expression by ectopic expression or knockdown selectively modulated IL-5R but not GM-CSF receptor signaling, and severely affected IL-5-induced eosinophil differentiation from primary human CD34+ hematopoietic progenitor cells. We found syntenin up-regulated during eosinophilopoiesis but down-regulated during neutropoiesis. Syntenin forms complexes with multiple IL-5Ralpha chains, suggesting that syntenin-enhanced IL-5R output may result from stabilization of an IL-5-induced oligomeric receptor complex. These data demonstrate that cytokine-specific functions can be transduced by unique receptor alpha-chain-associating adapter proteins.

journal_name

Blood

journal_title

Blood

authors

Beekman JM,Verhagen LP,Geijsen N,Coffer PJ

doi

10.1182/blood-2009-03-208850

subject

Has Abstract

pub_date

2009-10-29 00:00:00

pages

3917-27

issue

18

eissn

0006-4971

issn

1528-0020

pii

blood-2009-03-208850

journal_volume

114

pub_type

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