A new feature of Mpl receptor: ligand-induced transforming activity in FRE rat fibroblasts.
Oncogene
; 19(16): 2033-42, 2000 Apr 13.
Article
en En
| MEDLINE
| ID: mdl-10803464
Mpl is the receptor for thrombopoietin, the primary regulator of platelet production by megakaryocytes. Upon stimulation by its ligand, Mpl receptor induces proliferation and differentiation of hematopoietic cell lines of various origins. In this paper, we show that Mpl is also able to transform FRE rat fibroblasts in the presence of MGDF (pegylated Megakaryocyte Growth and Development Factor), a modified form of its ligand. We also demonstrate that upon MGDF stimulation Mpl receptor activates the classical transduction pathways described for hematopoietic cell lines in FRE cells. Introduction of Mpl deletion mutants in FRE cells allowed us to demonstrate that the C-terminal region of the Mpl intracytoplasmic domain, which is involved in hematopoietic differentiation, is necessary for the transformation process. Within that region, site-directed mutagenesis showed that the Y112 residue, which is required for Shc phosphorylation, is essential for rat fibroblast transformation by Mpl/MGDF, suggesting the involvement of Shc in Mpl-mediated transformation. Interestingly, we showed that transformation correlated with strong and sustained MAPK activation. Neither Jak2, Stat3 nor Stat5 phosphorylation was sufficient to induce the transformation process. Taken altogether, our results suggest the oncogenicity of Mpl in fibroblastic cells in the presence of its ligand.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Transformación Celular Neoplásica
/
Proteínas Proto-Oncogénicas
/
Receptores de Citocinas
/
Proteínas Adaptadoras del Transporte Vesicular
/
Proteínas Adaptadoras Transductoras de Señales
/
Proteínas de la Leche
/
Proteínas de Neoplasias
Idioma:
En
Revista:
Oncogene
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Año:
2000
Tipo del documento:
Article
País de afiliación:
Francia
Pais de publicación:
Reino Unido