Effects of calreticulin deficiency and myeloproliferative neoplasm (MPN)-linked mutation on cellular calcium signaling.

ABSTRACT: Calreticulin (CRT) is an endoplasmic reticulum (ER) chaperone containing multiple low affinity calcium-binding sites in its acidic C-terminal domain. Somatic mutations of the CRT gene (CALR) that are drivers of a subset of myeloproliferative neoplasms (MPN) alter the C-terminal domain. Perturbations in ER calcium storage and signaling are reported for an MPN type I mutant, CRT_Del52, and have been linked to disease pathogenesis. The effects of the mutations on calcium binding are, however, yet to be quantified. Using recombinant purified proteins, we found that residues 340-349 in the CRT C-terminal domain, conserved in both the wild-type CRT and CRT_Del52, are major contributors to low affinity calcium binding measured using isothermal titration calorimetry (ITC

SUBMITTER: Tagoe INA 

PROVIDER: S-EPMC12262281 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature