Calcium‐dependent methylation by PRMT1 promotes erythroid differentiation through the p38α MAPK pathway

Protein arginine methyltransferase 1 (PRMT1) stimulates erythroid differentiation, but the signaling events upstream are yet to be identified. Ca 2+ plays crucial roles during erythroid differentiation. Here, we show that Ca 2+ enhances methylation during induced erythroid differentiation and that Ca 2+ directly upregulates the catalytic activity of recombinant PRMT1 by increasing V max toward the substrate heterogeneous nuclear ribonucleoprotein A2. We demonstrate that PRMT1 is essential and responsible for the effect of Ca 2+ on differentiation. Depletion of Ca 2+ suppresses PRMT1‐mediated activation of p38α and p38α‐stimulated differentiation. Furthermore, Ca 2+ stimulates methylation of p38α by PRMT1. This study uncovers a novel regulatory mechanism for PRMT1 by Ca 2+ and identifies the PRMT1/p38α axis as an intracellular mediator of Ca 2+ signaling during erythroid differentiation.