Cytokine-Regulated Phosphorylation and Activation of TET2 by JAK2 in Hematopoiesis.

ABSTRACT: Even though the Ten-eleven translocation (TET) enzymes catalyze the generation of 5-hydroxymethylcytosines required for lineage commitment and subsequent differentiation of stem cells into erythroid cells, the mechanisms that link extracellular signals to TET activation and DNA hydroxymethylation are unknown. We demonstrate that hematopoietic cytokines phosphorylate TET2, leading to its activation in erythroid progenitors. Specifically, cytokine receptor-associated JAK2 phosphorylates TET2 at tyrosines 1939 and 1964. Phosphorylated TET2 interacts with the erythroid transcription factor KLF1, and this interaction with TET2 is increased upon exposure to erythropoietin. The activating JAK2^V617F mutation seen in myeloproliferative disease patient samples and in mouse models is assoc

SUBMITTER: Jeong JJ 

PROVIDER: S-EPMC6697164 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature