biostudies-literatureUnknown49(10)Faiz MThis study was supported by Leukemia & Blood Cancer New Zealand (to Elizabeth C. Ledgerwood). Mifra Faiz was supported by a University of Otago Doctoral Scholarship.Calreticulin is a multifunctional protein found in the endoplasmic reticulum lumen that is important for calcium homeostasis and glycoprotein folding. Mutations in exon 9 of the CALR gene are the second most common genetic cause of myeloproliferative neoplasms. CALR-mutated megakaryocyte proliferation in myeloproliferative neoplasms involves cytokine-independent constitutive activation of JAK/STAT signaling caused by binding of mutant calreticulin to the thrombopoietin receptor. However, whether the partial or complete removal of wildtype calreticulin from the endoplasmic reticulum has additional effects on megakaryocyte biology is not clear. To explore the impact of calreticulin mutations independent of thrombopoietin receptor signaling we generated type 1-like CALR mutations in K-562 celCell biology international1262-1273https://www.ebi.ac.uk/biostudies/studies/S-EPMC12445808biostudies-literatureCALR Type 1-Like Mutations Increase Endoplasmic Reticulum Free Ca<sup>2+</sup> and Induce ERK1/2 Activation Independent of Thrombopoietin Receptor Activation.PMC12445808Faiz MDunstan-Harrison CLedgerwood ECfalseCALR Type 1-Like Mutations Increase Endoplasmic Reticulum Free Ca<sup>2+</sup> and Induce ERK1/2 Activation Independent of Thrombopoietin Receptor Activation.Calreticulin is a multifunctional protein found in the endoplasmic reticulum lumen that is important for calcium homeostasis and glycoprotein folding. Mutations in exon 9 of the CALR gene are the second most common genetic cause of myeloproliferative neoplasms. CALR-mutated megakaryocyte proliferation in myeloproliferative neoplasms involves cytokine-independent constitutive activation of JAK/STAT signaling caused by binding of mutant calreticulin to the thrombopoietin receptor. However, whether the partial or complete removal of wildtype calreticulin from the endoplasmic reticulum has additional effects on megakaryocyte biology is not clear. To explore the impact of calreticulin mutations independent of thrombopoietin receptor signaling we generated type 1-like CALR mutations in K-562 cel2025-01-01T00:00:00Z2025 Oct2026-06-03T14:39:24.649Z2026-05-29T03:05:33.701ZS-EPMC124458084058664110.1002/cbin.70053