Ontology highlight
ABSTRACT:
SUBMITTER: Lupardus PJ
PROVIDER: S-EPMC4050602 | biostudies-literature | 2014 Jun
REPOSITORIES: biostudies-literature
Lupardus Patrick J PJ Ultsch Mark M Wallweber Heidi H Bir Kohli Pawan P Johnson Adam R AR Eigenbrot Charles C
Proceedings of the National Academy of Sciences of the United States of America 20140519 22
Janus kinases (JAKs) are receptor-associated multidomain tyrosine kinases that act downstream of many cytokines and interferons. JAK kinase activity is regulated by the adjacent pseudokinase domain via an unknown mechanism. Here, we report the 2.8-Å structure of the two-domain pseudokinase-kinase module from the JAK family member TYK2 in its autoinhibited form. We find that the pseudokinase and kinase interact near the kinase active site and that most reported mutations in cancer-associated JAK ...[more]