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Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development
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C-Cbl regulates c-MPL receptor trafficking and its internalization

Melanie Märklin1, Claudia Tandler1, Hans-Georg Kopp2

  • 1Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), German Cancer Research Centre (DKFZ), University Hospital Tübingen, Tübingen, Germany.

Journal of Cellular and Molecular Medicine
|September 21, 2020
PubMed

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-Cblfl/fl Pf4Cre 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.

Keywords:
C-Cblc-MPLmegakaryocytesplateletsthrombocytosis

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