The Neurobeachin-like 2 Protein Regulates Mast Cell Homeostasis.
J Immunol
; 199(8): 2948-2957, 2017 10 15.
Article
en En
| MEDLINE
| ID: mdl-28887433
ABSTRACT
The neurobeachin-like 2 protein (Nbeal2) belongs to the family of beige and Chediak-Higashi (BEACH) domain proteins. Loss-of-function mutations in the human NBEAL2 gene or Nbeal2 deficiency in mice cause gray platelet syndrome, a bleeding disorder characterized by macrothrombocytopenia, splenomegaly, and paucity of α-granules in megakaryocytes and platelets. We found that in mast cells, Nbeal2 regulates the activation of the Shp1-STAT5 signaling axis and the composition of the c-Kit/STAT signalosome. Furthermore, Nbeal2 mediates granule formation and restricts the expression of the transcription factors, IRF8, GATA2, and MITF as well as of the cell-cycle inhibitor p27, which are essential for mast cell differentiation, proliferation, and cytokine production. These data demonstrate the relevance of Nbeal2 in mast cells above and beyond granule biosynthesis.
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1
Bases de datos:
MEDLINE
Asunto principal:
Megacariocitos
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Proteínas Sanguíneas
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Gránulos Citoplasmáticos
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Síndrome de Plaquetas Grises
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Mastocitos
Límite:
Animals
Idioma:
En
Revista:
J Immunol
Año:
2017
Tipo del documento:
Article