The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
The pseudokinase domain of JAK2 is a dual-specificity protein kinase that negatively regulates cytokine signaling
Open accessAbstract
Human JAK2 tyrosine kinase mediates signaling through numerous cytokine receptors. The JAK2 JH2 domain functions as a negative regulator and is presumed to be a catalytically inactive pseudokinase, but the mechanism(s) for its inhibition of JAK2 remains unknown. 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. Notably, different MPN mutations abrogated JH2 activity in cells, and in MPN (V617F) patient cells phosphorylation of Tyr570 was reduced, suggesting that loss of JH2 activity contributes to the pathogenesis of MPNs. These results identify the catalytic activity of JH2 as a previously unrecognized mechanism to control basal activity and signaling of JAK2.
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Cites
In-gel digestion for mass spectrometric characterization of proteins and proteomes
Shevchenko, A., Tomas, H., Havli, J., Olsen, J. V., & Mann, M. (2006) · Nature Protocols · doi:10.1038/nprot.2006.468 · Cited by 4,942
Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders
Baxter, E. J., Scott, L. M., Campbell, P. J., East, C., Fourouclas, N., Swanton, S., Vassiliou, G. S., Bench, A. J., Boyd, E. M., Curtin, N., et al. (2005) · The Lancet · doi:10.1016/s0140-6736(05)71142-9 · Cited by 3,548
A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera
James, C., Ugo, V., Le Couédic, J.-P., Staerk, J., Delhommeau, F., Lacout, C., Garçon, L., Raslova, H., Berger, R., Bennaceur-Griscelli, A., et al. (2005) · Nature · doi:10.1038/nature03546 · Cited by 3,544
A Gain-of-Function Mutation of JAK2 in Myeloproliferative Disorders
Kralovics, R., Passamonti, F., Buser, A. S., Teo, S.-S., Tiedt, R., Passweg, J. R., Tichelli, A., Cazzola, M., & Skoda, R. C. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa051113 · Cited by 3,470
Self-citationRegulation of JAK–STAT signalling in the immune system
Shuai, K., & Liu, B. (2003) · Nature Reviews Immunology · doi:10.1038/nri1226 · Cited by 1,372
JAK2 Exon 12 Mutations in Polycythemia Vera and Idiopathic Erythrocytosis
Scott, L. M., Tong, W., Levine, R. L., Scott, M. A., Beer, P. A., Stratton, M. R., Futreal, P. A., Erber, W. N., McMullin, M. F., Harrison, C. N., et al. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa065202 · Cited by 1,276
Protein Tyrosine Kinase Structure and Function
Hubbard, S. R., & Till, J. H. (2000) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.69.1.373 · Cited by 1,171
Self-citationYamaoka, K., Saharinen, P., Pesu, M., Holt, V. E., Silvennoinen, O., & O'Shea, J. J. (2004) · Genome Biology · doi:10.1186/gb-2004-5-12-253 · Cited by 635
Self-citationHighly selective enrichment of phosphorylated peptides using titanium dioxide
Thingholm, T. E., Jørgensen, T. J. D., Jensen, O. N., & Larsen, M. R. (2006) · Nature Protocols · doi:10.1038/nprot.2006.185 · Cited by 618
Self-citationImada, K., & Leonard, W. J. (2000) · Molecular Immunology · doi:10.1016/s0161-5890(00)00018-3 · Cited by 610 · cited 1×
“2099" language="eng" relation="no"> JAK2 belongs to the Janus family of cytoplasmic tyrosine kinases ( JAK1 – JAK3 , TYK2 ) and functions as a crucial mediator of signaling for hematopoietic cytokines and hormones such as erythropoietin ( Epo ), thrombopoietin ( Tpo ), interferon-γ ( IFN-γ ), several interleukins, gro…”
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Villarino, A. V., Kanno, Y., & O'Shea, J. J. (2017) · Nature Immunology · doi:10.1038/ni.3691 · Cited by 1,221
The Pseudokinase MLKL Mediates Necroptosis via a Molecular Switch Mechanism
Murphy, J. M., Czabotar, P. E., Hildebrand, J. M., Lucet, I. S., Zhang, J.-G., Alvarez-Diaz, S., Lewis, R., Lalaoui, N., Metcalf, D., Webb, A. I., et al. (2013) · Immunity · doi:10.1016/j.immuni.2013.06.018 · Cited by 1,220
Banerjee, S., Biehl, A., Gadina, M., Hasni, S., & Schwartz, D. M. (2017) · Drugs · doi:10.1007/s40265-017-0701-9 · Cited by 1,206
The molecular details of cytokine signaling via the JAK/STAT pathway
Morris, R., Kershaw, N. J., & Babon, J. J. (2018) · Protein Science · doi:10.1002/pro.3519 · Cited by 943
Metadata
- Authors
- Ungureanu, D., Wu, J., Pekkala, T., Niranjan, Y., Young, C., Jensen, O. N., Xu, C.-F., Neubert, T. A., Skoda, R. C., Hubbard, S. R., & Silvennoinen, O.
- Venue
- Nature Structural & Molecular Biology
- Published
- 2011-08-14
- Volume
- 18
- Issue
- 9
- Pages
- 971-976
- ISSN
- 1545-9985 (ISSN-L)
- 1545-9993
- OpenAlex
- W1966969980
- Cited by
- 276
- References
- 39
- FWCI
- 12.82
- Type
- journal article
- Language
- en
- Open access
- green
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- Ungureanu, D., Wu, J., Pekkala, T., Niranjan, Y., Young, C., Jensen, O. N., Xu, C.-F., Neubert, T. A., Skoda, R. C., Hubbard, S. R., & Silvennoinen, O. (2011). The pseudokinase domain of JAK2 is a dual-specificity protein kinase that negatively regulates cytokine signaling. Nature Structural & Molecular Biology. https://doi.org/10.1038/nsmb.2099
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