The JAK2V617F Tyrosine Kinase Mutation in Myeloproliferative Disorders: Status Report and Immediate Implications for Disease Classification and Diagnosis

Tefferi, Ayalew; Gilliland, D. Gary
July 2005
Mayo Clinic Proceedings;Jul2005, Vol. 80 Issue 7, p947
Academic Journal
Janus kinase 2 (JAK2) is a cytoplasmic protein-tyrosine kinase that catalyzes the transfer of the y-phosphate group of adenosine triphosphate to the hydroxyl groups of specific tyrosine residues In signal transduction molecules. JAK2 mediates signaling downstream of cytokine receptors after Ilgand4nduced autophosphorylation of both receptor and enzyme. The main downstream effectors of JAK2 are a family of transcription factors known as signal transducers and activators of transcription (STAT) proteins. The myeloproliferative disorders (MPD), a subgroup of myeloid malignancies, are clonal stem cell diseases characterized by an expansion of morphologically mature granulocyte, erythroid, megakaryocyte, or monocyte lineage cells. Among the traditionally classified MPD, the disease-causing mutation has been delineated, thus far, for only chronic myeloid leukemia (le, bcr/abl). In the past 3 months, 7 different studies have independently described a close association between an activating JAK2 mutation (JAK2V617F) and the classic bcr/abl-negative MPD (ie, polycythemia vera, essential thrombocythemia, myelofibrosis with myeloid metaplasia) as we, as the less frequent occurrence of the same mutation In both atypical MPD and the myelodysplastic syndrome. The particular finding is consistent with previous observations that have implicated the JAK/STAT signal transduction pathway in the pathogenesis of bcr/abl-negative MPD, Including the phenotype of growth factor independence and/or hypersensitivity. The current article summarizes this new information and discusses its implications for both classification and diagnosis of MPD.


Related Articles

  • Protein tyrosine kinase Pyk2 mediates the Jak-dependent activation of MAPK and Stat1 in IFN-?, but not IFN-a, signaling. Takaoka, Akinori; Tanaka, Nobuyuki; Mitani, Yukiko; Miyazaki, Tadaaki; Fujii, Hodaka; Sato, Mitsuharu; Kovarik, Pavel; Decker, Thomas; Schlessinger, Joseph; Taniguchi, Tadatsugu // EMBO Journal;5/1/99, Vol. 18 Issue 9, p2480 

    Two distinct types of interferon, IFN-α/β and IFN-γ, commonly exhibit antiviral activities by transmitting signals to the interior of the cell via their homologous receptors. Receptor stimulation results in the activation of distinct combinations of Janus family protein tyrosine kinases...

  • Tyrosine Kinase Inhibitors. Natoli, C.; Perrucci, B.; Perrotti, F.; Falchi, L.; Iacobelli, S. // Current Cancer Drug Targets;Aug2010, Vol. 10 Issue 5, p462 

    No abstract available.

  • RAS/RAF/MEK Inhibitors in Oncology. Rusconi, P.; Caiola, E.; Broggini, M. // Current Medicinal Chemistry;Mar2012, Vol. 19 Issue 8, p1164 

    The RAS/RAF/MEK signaling pathway plays a central role in mediating both proliferation and survival of cancer cells. These proteins are a group of serine/threonine kinases activated in response to a variety of extracellular stimuli and mediate signal transduction from the cell surface towards...

  • Centrosome-Kinase Fusions Promote Oncogenic Signaling and Disrupt Centrosome Function in Myeloproliferative Neoplasms. Lee, Joanna Y.; Hong, Wan-Jen; Majeti, Ravindra; Stearns, Tim // PLoS ONE;Mar2014, Vol. 9 Issue 3, p1 

    Chromosomal translocations observed in myeloproliferative neoplasms (MPNs) frequently fuse genes that encode centrosome proteins and tyrosine kinases. This causes constitutive activation of the kinase resulting in aberrant, proliferative signaling. The function of centrosome proteins in these...

  • Integrating signals from RTKs to ERK/MAPK. McKay, M. M.; Morrison, D. K. // Oncogene;5/14/2007, Vol. 26 Issue 22, p3113 

    Signals received at the cell surface must be properly transmitted to critical targets within the cell to achieve the appropriate biological response. This process of signal transduction is often initiated by receptor tyrosine kinases (RTKs), which function as entry points for many extracellular...

  • PKC and the control of localized signal dynamics. Rosse, Carine; Linch, Mark; Kermorgant, Stéphanie; Cameron, Angus J. M.; Boeckeler, Katrina; Parker, Peter J. // Nature Reviews Molecular Cell Biology;Feb2010, Vol. 11 Issue 2, p103 

    Networks of signal transducers determine the conversion of environmental cues into cellular actions. Among the main players in these networks are protein kinases, which can acutely and reversibly modify protein functions to influence cellular events. One group of kinases, the protein kinase C...

  • Hsp90 restrains ErbB-2/HER2 signalling by limiting heterodimer formation. Citri, Ami; Gan, Judith; Mosesson, Yaron; Vereb, Gyorgi; Szollosi, Janos; Yarden, Yosef // EMBO Reports;Dec2004, Vol. 5 Issue 12, p1165 

    ErbB-2/HER2 is an oncogenic tyrosine kinase that regulates a signalling network by forming ligand-induced heterodimers with several growth factor receptors of the ErbB family. Hsp90 and co-chaperones regulate degradation of ErbB-2 but not other ErbB members. Here, we report that the role of...

  • Current Status and Future Prospects of C1 Domain Ligands as Drug Candidates. Gennäs, Gustav Boije af; Talman, Virpi; Yli-Kauhaluoma, Jari; Tuominen, Raimo K; Ekokoski, Elina // Current Topics in Medicinal Chemistry;Jun2011, Vol. 11 Issue 11, p1370 

    The second messenger diacylglycerol (DAG) plays a central role in the signal transduction of G-protein coupled receptors and receptor tyrosine kinases by binding to C1 domain of effector proteins. C1 domain was first identified in protein kinase C (PKC) which comprises a family of ten isoforms...

  • Effect of the SH3-SH2 domain linker sequence on the structure of Hck kinase. Meiselbach, Heike; Sticht, Heinrich // Journal of Molecular Modeling;Aug2011, Vol. 17 Issue 8, p1927 

    The coordination of activity in biological systems requires the existence of different signal transduction pathways that interact with one another and must be precisely regulated. The Src-family tyrosine kinases, which are found in many signaling pathways, differ in their physiological function...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics