The abundance of surface GH receptor (GHR) is an important determinant of cellular GH sensitivity and is regulated at both transcriptional and posttranscriptional levels. In previous studies of GHR-expressing Janus kinase 2 (JAK2)-deficient human fibrosarcoma cells (gamma2A-GHR), we demonstrated that stable transfection with JAK2 resulted in increased steady-state levels of mature GHR (endoH-re...

Amentoflavone has been identified as a JAK2 inhibitor by structure-based virtual screening of a natural product library. In silico optimization using the DOLPHIN model yielded analogues with enhanced potency against JAK2 activity and HCV activity in cellulo. Molecular modeling and kinetic experiments suggested that the analogues may function as Type II inhibitors of JAK2.

JAK inhibitors have been developed following the discovery of the JAK2V617F in 2005 as the driver mutation of the majority of non- BCR-ABL1 myeloproliferative neoplasms (MPNs). Subsequently, the search for JAK2 inhibitors continued with the discovery that the other driver mutations ( CALR and MPL) also exhibited persistent JAK2 activation. Several type I ATP-competitive JAK inhibitors with diff...

OBJECTIVE While the somatic mutation of Janus Kinase 2 (JAK2) and the thrombopoietin receptor (c-MPL) gene are thought to affect the pathogenesis of bcr/abl negative chronic myeloproliferative neoplasm (MPN), the relationship between the mutation and the clinical features remain obscure. METHODS The mutation status of these genes in granulocytes, platelets, T-cells, and erythroid colonies (BF...

1. Baxter EJ, Scott LM, Campbell PJ, et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. 2005;365:10541061. 2. Levine RL, Wadleigh M, Cools J, et al. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell. 2005;7:387-397. 3. James C, Ugo V, Le Couedic ...

Previous studies have suggested that the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway is involved in hyperglycemia‑induced lung injury. The present study aimed to investigate the roles of suppressor of cytokine signaling3 (SOCS3) in the regulation of JAK2/STAT3 activation following high glucose (HG) treatment in A549 human pulmonary epithelial cells. Cell...

UNLABELLED Janus kinase 2 (JAK2) is a protein tyrosine kinase central to a multitude of cellular processes. Here, a novel model of JAK2 regulation and activation is proposed. In the JAK2 dimer, instead of being auto-inhibited by its own JH2 domain, inhibition comes from the JH2 domain of the partnering JAK2 monomer. Upon ligand binding, the receptor undergoes a conformational rotation that is p...

BACKGROUND/AIMS The diagnosis of an underlying myeloproliferative neoplasm (MPN) is often problematic in patients with Budd Chiari syndrome (BCS) or portal vein thrombosis (PVT). This study aimed to assess the diagnostic value of the JAK2 gene V617F gain-of-function mutation for MPN in splanchnic vein thrombosis patients. MATERIALS AND METHODS One hundred eleven patients (80 with PVT, 27 with...

Previous reports have shown that active JAK2 contributes to T cell acute lymphoblastic leukaemia (T-ALL) development and that JAK inhibitors may be a potential treatment for T-ALL. In the current study, the JAK2 inhibitor TG101209 was used to treat T-ALL cell lines and primary T-ALL cells. The effects of TG101209 on T-ALL cells were determined, and the signaling proteins related to cell growth,...

Pseudokinases lack conserved motifs typically required for kinase activity. Nearly half of pseudokinases bind ATP, but only few retain phosphotransfer activity, leaving the functional role of nucleotide binding in most cases unknown. Janus kinases (JAKs) are nonreceptor tyrosine kinases with a tandem pseudokinase-kinase domain configuration, where the pseudokinase domain (JAK homology 2, JH2) h...