نتایج جستجو برای: jak2

تعداد نتایج: 4657  

Journal: :Molecular cancer therapeutics 2010
Fabienne Baffert Catherine H Régnier Alain De Pover Carole Pissot-Soldermann Gisele A Tavares Francesca Blasco Josef Brueggen Patrick Chène Peter Drueckes Dirk Erdmann Pascal Furet Marc Gerspacher Marc Lang David Ledieu Lynda Nolan Stephan Ruetz Joerg Trappe Eric Vangrevelinghe Markus Wartmann Lorenza Wyder Francesco Hofmann Thomas Radimerski

The recent discovery of an acquired activating point mutation in JAK2, substituting valine at amino acid position 617 for phenylalanine, has greatly improved our understanding of the molecular mechanism underlying chronic myeloproliferative neoplasms. Strikingly, the JAK2(V617F) mutation is found in nearly all patients suffering from polycythemia vera and in roughly every second patient sufferi...

Journal: :The Journal of biological chemistry 2002
Pipsa Saharinen Olli Silvennoinen

Janus (Jak) tyrosine kinases contain a tyrosine kinase (JH1) domain adjacent to a catalytically inactive pseudokinase domain (JH2). The JH2 domain has been implicated in regulation of Jak activity, but its function remains poorly understood. Here, we found that the JH2 domain negatively regulates the activity of Jak2 and Jak3. Deletion of JH2 resulted in increased tyrosine phosphorylation of th...

Journal: :Blood 2013
Koichi Takahashi Keyur P Patel Hagop Kantarjian Rajyalakshmi Luthra Sherry Pierce Jorge Cortes Srdan Verstovsek

Detection of the JAK2 p.V617F mutation and measurement of its allele burden can be performed using both peripheral blood (PB) and bone marrow (BM) samples from patients with myeloproliferative neoplasms (MPNs). However, the diagnostic accuracy of detecting the JAK2 p.V617F mutation and quantifying its allele burden in PB and BM samples has not been systematically compared. We retrospectively an...

2017
Kyoung Bin Yoon Sung Yun Cho Su Jin An Kyeong Ryang Park Hyo Jeong Lee Hae Sung Yoon Sun-Mi Lee Yong-Chul Kim Sun-Young Han

Janus kinase 2 (JAK2) is a non-receptor tyrosine kinase that regulates the signal transducer and activator of transcription (STAT) signaling pathway. Deregulation of JAK2 signaling has previously been observed in hematologic malignancies, including erythroleukemia. In the present study, an aminopyridine derivative compound, KRC-180, exhibited direct inhibition of the JAK2 protein at the catalyt...

Journal: :JCI insight 2017
Tharini Sivasubramaniyam Stephanie A Schroer Angela Li Cynthia T Luk Sally Yu Shi Rickvinder Besla David W Dodington Adam H Metherel Alex P Kitson Jara J Brunt Joshua Lopes Kay-Uwe Wagner Richard P Bazinet Michelle P Bendeck Clinton S Robbins Minna Woo

Atherosclerosis is considered both a metabolic and inflammatory disease; however, the specific tissue and signaling molecules that instigate and propagate this disease remain unclear. The liver is a central site of inflammation and lipid metabolism that is critical for atherosclerosis, and JAK2 is a key mediator of inflammation and, more recently, of hepatic lipid metabolism. However, precise e...

2017
Ioannis Panagopoulos Ludmila Gorunova Signe Spetalen Assia Bassarova Klaus Beiske Francesca Micci Sverre Heim

Acquired mutations were recently described in cutaneous T-cell lymphomas for the JAK1, JAK3, STAT3, and STAT5B genes of the JAK-STAT pathway. In the present study, RNA-sequencing of a primary cutaneous CD4 positive T-cell lymphoma carrying a three-way t(9;13;16)(p24;q34;p11) chromosome translocation showed that JAK2 from chromosome band 9p24 was rearranged and fused to a novel partner gene, ATX...

Journal: :Blood 1998
N Ogata T Kouro A Yamada M Koike N Hanai T Ishikawa K Takatsu

The human interleukin-5 receptor (hIL-5R) consists of a unique alpha subunit (hIL-5Ralpha) and a common beta subunit (betac) that activate two Janus kinases (JAK1 and JAK2) and a signal transducer and activator of transcription (STAT5). The precise stoichiometry of the hIL-5R subunits and the role of JAK kinases used in IL-5 signaling were investigated. We analyzed the interaction between hIL-5...

Journal: :The Journal of clinical investigation 1999
C Bousquet C Susini S Melmed

Leukemia inhibitory factor (LIF) is a pleiotropic cytokine that stimulates the hypothalamo-pituitary-adrenal (HPA) axis through JAK-STAT activation. We show here that LIF-induced JAK2 and STAT3 tyrosine phosphorylation is transient, disappearing within 20 and 40 minutes, respectively. LIF activates the SH2 domain-containing tyrosine phosphatase, SHP-1, with maximal stimulation observed at 30 mi...

Journal: :Journal of immunology 2005
Yulia Nefedova Pingyan Cheng Daniele Gilkes Michelle Blaskovich Amer A Beg Said M Sebti Dmitry I Gabrilovich

Signaling via Jak2/STAT3 is critically important for normal dendritic cell (DC) differentiation. In addition, we have previously demonstrated that hyperactivation of the Jak2/STAT3 pathway induced by tumor-derived factors (TDF) may be responsible for abnormal DC differentiation in cancer. In this study, using a novel selective inhibitor of Jak2/STAT3, JSI-124, we investigated the mechanism of t...

Journal: :Blood 2010
Priya Koppikar Omar Abdel-Wahab Cyrus Hedvat Sachie Marubayashi Jay Patel Aviva Goel Nicole Kucine Jeffrey R Gardner Andrew P Combs Kris Vaddi Patrick J Haley Timothy C Burn Mark Rupar Jacqueline F Bromberg Mark L Heaney Elisa de Stanchina Jordan S Fridman Ross L Levine

The discovery of JAK2 and MPL mutations in patients with myeloproliferative neoplasms (MPNs) provided important insight into the genetic basis of these disorders and led to the development of JAK2 kinase inhibitors for MPN therapy. Although recent studies have shown that JAK2 kinase inhibitors demonstrate efficacy in a JAK2V617F murine bone marrow transplantation model, the effects of JAK2 inhi...

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