Oncogenic CALR mutant C-terminus mediates dual binding to the thrombopoietin receptor triggering complex dimerization and activation

In myeloproliferative neoplasms, frameshift mutants of calreticulin turn into rogue cytokines by inducing constitutive activation of the Thrombopoietin Receptor (TpoR). Here, the authors define how mutant calreticulin acquires specificity for TpoR binding and triggers its constitutive activation.

Bibliographic Details
Main Authors: Nicolas Papadopoulos, Audrey Nédélec, Allison Derenne, Teodor Asvadur Şulea, Christian Pecquet, Ilyas Chachoua, Gaëlle Vertenoeil, Thomas Tilmant, Andrei-Jose Petrescu, Gabriel Mazzucchelli, Bogdan I. Iorga, Didier Vertommen, Stefan N. Constantinescu
Format: Article
Language:English
Published: Nature Portfolio 2023-04-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-023-37277-3
Description
Summary:In myeloproliferative neoplasms, frameshift mutants of calreticulin turn into rogue cytokines by inducing constitutive activation of the Thrombopoietin Receptor (TpoR). Here, the authors define how mutant calreticulin acquires specificity for TpoR binding and triggers its constitutive activation.
ISSN:2041-1723