Rab27b regulates c-kit expression by controlling the secretion of stem cell factor.
Biochem Biophys Res Commun
; 419(2): 368-73, 2012 Mar 09.
Article
en En
| MEDLINE
| ID: mdl-22349512
ABSTRACT
Rab27b, a subfamily of Rab27 small GTPases, was originally identified in platelets. However, the role of Rab27b in megakaryocytic lineage cells remains unknown. Here, using a human megakaryoblastic cell line, CMK, we show that Rab27b negatively regulates c-kit-expression. We found that transfection of shRNA-Rab27b into CMK cells led to specific increase in the amount of the receptor-type tyrosine kinase c-kit. To elucidate the molecular mechanisms by which Rab27b regulates c-kit expression, we analyzed the dynamics of c-kit by the stimulation with its ligand, stem cell factor (SCF). We found that cell surface expression of c-kit was promptly reduced and rapidly degraded in both CMK and Rab27b-knockdown CMK cells. Pretreatment with a lysosome inhibitor bafilomycin suppressed the degradation of c-kit, indicating that c-kit expression is controlled by SCF-induced endolysosomal degradation system. We therefore focused on the potential involvement of SCF in Rab27b-mediated effects on c-kit expression levels. We found that autocrine secretion of SCF was downregulated in Rab27b-knockdown cells as compared with parental CMK cells. These results suggest that Rab27b negatively regulates the cell surface expression of c-kit via secretion of SCF and that ligation of SCF leads to the endolysosomal degradation system of c-kit.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Factor de Células Madre
/
Proteínas Proto-Oncogénicas c-kit
/
Proteínas de Unión al GTP rab
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Año:
2012
Tipo del documento:
Article