2022年6月2日 · JAK2 is a non-receptor tyrosine kinase that regulates hematopoiesis through the JAK-STAT pathway. The pseudokinase domain (JH2) is an important regulator of the activity of the kinase domain (JH1). V617F mutation in JH2 has been associated with the pathogenesis of various myeloproliferative neoplasms, but JAK2 JH2 has been poorly explored as a ...

哺乳动物有4个jak同源基因，包括jak1、jak2、jak3和tyk2 四个成员。 JAKs的分子量在120-140kDa之间，每个JAKs成员具有7个保守的JH结构域，无跨膜结构域 。 JAK的特征是双激酶结构域： C末端第一个结构域JH1具有酪氨酸激酶活性，其前面是一个假激酶结构域（JH2）。

2024年3月8日 · JH2 was originally identified in JAK2 as a key regulator of activation that functions in a dualistic fashion; JH2 maintains JAKs in an inactive state in the absence of cytokine stimulation (autoinhibitory activity), but it is also required for ligand-induced activation (stimulatory activity) (16–18).

The JAK2 JH2 Pseudokinase Domain Inhibitor Screening Assay Kit is designed for screening and profiling small molecules that displace the fluorescently labeled probe (JH2 probe 1) from the JH2 domain of JAK2. The assay is based on the competition of the test compound with the JH2 probe for binding to purified JAK2 JH2.

Jak2 possesses a pseudokinase domain (JH2) and a tyrosine kinase domain (JH1). Through unknown mechanisms, JH2 regulates the catalytic activity of JH1, and hyperactivating mutations in the JH2 region of human Jak2 are causative for myeloproliferative neoplasms (MPNs). We showed previously that Jak2 JH2 is in fact catalytically active.

JAK2 possesses a pseudokinase domain (JH2) and a tyrosine kinase domain (JH1). Through unknown mechanisms, JH2 regulates the catalytic activity of JH1, and hyperactivating mutations in the JH2 region of human JAK2 cause myeloproliferative neoplasms (MPNs). We showed previously that JAK2 JH2 is, in fact, catalytically active.

2020年5月28日 · The present focus is on the discovery of molecules that may regulate the activity of JAK2 by selective binding to the JAK2 pseudokinase domain, JH2. Specifically, the Val617Phe mutation in JH2 stimulates the activity of the adjacent kinase domain (JH1) resulting in myeloproliferative disorders.

Probe molecules that covalently modify the JAK2 pseudokinase domain (JH2) are reported. Selective targeting of JH2 domains over the kinase (JH1) domains is a necessary feature for ligands intended to evaluate JH2 domains as therapeutic targets.

2025年3月25日 · It downregulated JAK2 and STAT3 phosphorylation and stimulated autophagy in leukemic cells. In vivo, SAR317461 reduced peripheral blood leukocyte counts and prolonged survival in AML mice. ... For instance, the JAK2V617F mutation in the JH2 domain results in constitutive activation of the JH1 kinase domain, enhancing JAK and STAT signaling ...

Mutations in JH2 lead to increased JAK2 activity contributing to myeloproliferative neoplasms (MPNs). Here, we show that JH2 is a dual-specificity protein kinase that phosphorylates two negative regulatory sites in JAK2, Ser523 and Tyr570. Inactivation of JH2 catalytic activity increased JAK2 basal activity and downstream signaling.