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Structural Insights into the Interaction of Heme with Protein Tyrosine Kinase JAK2 **
Author(s) -
Schmalohr Benjamin Franz,
Mustafa AlHassan M.,
Krämer Oliver H.,
Imhof Diana
Publication year - 2021
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.202000730
Subject(s) - heme , myeloproliferative disorders , biochemistry , janus kinase 2 , chemistry , hyperphosphorylation , microbiology and biotechnology , receptor tyrosine kinase , kinase , signal transduction , tyrosine kinase , biology , enzyme , immunology
Janus kinase 2 (JAK2) is the most important signal‐transducing tyrosine kinase in erythropoietic precursor cells. Its malfunction drives several myeloproliferative disorders. Heme is a small metal‐ion‐carrying molecule that is incorporated into hemoglobin in erythroid precursor cells to transport oxygen. In addition, heme is a signaling molecule and regulator of various biochemical processes. Here, we show that heme exposure leads to hyperphosphorylation of JAK2 in a myeloid cancer cell line. Two peptides identified in JAK2 are heme‐regulatory motifs and show low‐micromolar affinities for heme. These peptides map to the kinase domain of JAK2, which is essential for downstream signaling. We suggest these motifs to be the interaction sites of heme with JAK2, which drive the heme‐induced hyperphosphorylation. The results presented herein could facilitate the development of heme‐related pharmacological tools to combat myeloproliferative disorders.