JAK2V617F-mediated phosphorylation of PRMT5 downregulates its methyltransferase activity and promotes myeloproliferation. Academic Article uri icon

Overview

abstract

  • The JAK2V617F constitutively activated tyrosine kinase is found in most patients with myeloproliferative neoplasms. While examining the interaction between JAK2 and PRMT5, an arginine methyltransferase originally identified as JAK-binding protein 1, we found that JAK2V617F (and JAK2K539L) bound PRMT5 more strongly than did wild-type JAK2. These oncogenic kinases also acquired the ability to phosphorylate PRMT5, greatly impairing its ability to methylate its histone substrates, and representing a specific gain-of-function that allows them to regulate chromatin modifications. We readily detected PRMT5 phosphorylation in JAK2V617F-positive patient samples, and when we knocked down PRMT5 in human CD34+ cells using shRNA, we observed increased colony formation and erythroid differentiation. These results indicate that phosphorylation of PRMT5 contributes to the mutant JAK2-induced myeloproliferative phenotype.

publication date

  • February 15, 2011

Research

keywords

  • Down-Regulation
  • Janus Kinase 2
  • Protein Methyltransferases

Identity

PubMed Central ID

  • PMC4687747

Scopus Document Identifier

  • 79751486147

Digital Object Identifier (DOI)

  • 10.1016/j.ccr.2010.12.020

PubMed ID

  • 21316606

Additional Document Info

volume

  • 19

issue

  • 2