In:
The Journal of Immunology, The American Association of Immunologists, Vol. 199, No. 8 ( 2017-10-15), p. 2948-2957
Kurzfassung:
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.
Materialart:
Online-Ressource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.1700556
Sprache:
Englisch
Verlag:
The American Association of Immunologists
Publikationsdatum:
2017
ZDB Id:
1475085-5
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