C-Cbl Regulates C-MPL Receptor Trafficking and Its Internalization

Overview

Journal J Cell Mol Med

Specialties Cell Biology
Molecular Biology

Date 2020 Sep 21

PMID 32954656

Citations 6

Authors

Melanie Marklin

Claudia Tandler

Hans-Georg Kopp

Kyle L Hoehn

Leticia Quintanilla-Martinez

Oliver Borst

Martin R Muller

Sebastian J Saur

Affiliations

Soon will be listed here.

Abstract

Thrombocyte formation from megakaryocyte and their progenitor cells is tightly regulated by thrombopoietin (TPO) and its receptor c-MPL, thereby maintaining physiological functionality and numbers of circulating platelets. In patients, dysfunction of this regulation could cause thrombocytopenia or myeloproliferative syndromes. Since regulation of this pathway is still not completely understood, we investigated the role of the ubiquitin ligase c-Cbl which was previously shown to negatively regulated c-MPL signalling. We developed a new conditional mouse model using c-Cbl Pf4 mice and demonstrated that platelet-specific knockout of c-Cbl led to severe microthrombocytosis and impaired uptake of TPO and c-MPL receptor internalization. Furthermore, we characterized a constitutive STAT5 activation c-Cbl KO platelets. This study identified c-Cbl as a potential player in causing megakaryocytic and thrombocytic disorders.

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