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Pathology & Oncology Research
Published in: Pathology & Oncology Research 2/2019

01-04-2019 | Letter to the Editor

JAK Pseudokinase Domain Variants Highlight nRTK VUSs Identified with Next-Generation Sequencing in Solid Tumor Patients

Authors: Matthew K. Stein, Lindsay K. Morris, Mike G. Martin

Published in: Pathology & Oncology Research | Issue 2/2019

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Excerpt

Non-receptor tyrosine kinase (nRTK) pathways are aberrantly activated in cancer, and mutations in nRTKs have potential therapeutic and prognostic importance. Consisting of 10 families, the 32 known human nRTKs each include a TKD made of N and C-terminal lobes necessary for catalytic activity, as well as varying regulatory regions including Src homology 2 (SH2) and 3 (SH3), and in the case of the Janus kinases a PSKD which is also bi-lobed [1]. Tumor profiling with NGS enables the entire coding sequence of numerous genes to be evaluated, thus facilitating the identification of novel nsSNPs in nRTKs. …
Literature
1.
Lupardus PJ, Ultsch M, Wallweber H et al (2014) Structure of the pseudokinase-kinase domains from protein kinase TYK2 reveals a mechanism for Janus kinase (JAK) autoinhibition. Proc Natl Acad Sci U S A 111:8025–8030CrossRefPubMedPubMedCentral
2.
3.
Canté-Barrett K, Uitdehaag JC, Meijerink JP (2016) Structural modeling of JAK1 mutations in T-cell acute lymphoblastic leukemia reveals a second contact site between pseudokinase and kinase domains. Haematologica 101(5):e189–e191CrossRefPubMedPubMedCentral
4.
Perez C, Gonzalez-Rincon J, Onaindia A et al (2015) Mutated JAK kinases and deregulated STAT activity are potential therapeutic targets in cutaneous T-cell lymphoma. Haematologica 100(11):e450–e453CrossRefPubMedPubMedCentral
Metadata
Title
JAK Pseudokinase Domain Variants Highlight nRTK VUSs Identified with Next-Generation Sequencing in Solid Tumor Patients
Authors
Matthew K. Stein
Lindsay K. Morris
Mike G. Martin
Publication date
01-04-2019
Publisher
Springer Netherlands
Published in
Pathology & Oncology Research / Issue 2/2019
Print ISSN: 1219-4956
Electronic ISSN: 1532-2807
DOI
https://doi.org/10.1007/s12253-018-0443-3

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