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Publication : C-Cbl regulates c-MPL receptor trafficking and its internalization.

First Author  Märklin M Year  2020
Journal  J Cell Mol Med Volume  24
Issue  21 Pages  12491-12503
PubMed ID  32954656 Mgi Jnum  J:329627
Mgi Id  MGI:6719781 Doi  10.1111/jcmm.15785
Citation  Marklin M, et al. (2020) C-Cbl regulates c-MPL receptor trafficking and its internalization. J Cell Mol Med 24(21):12491-12503
abstractText  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(fl/fl) Pf4(Cre) 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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