Abstract
The Janus kinases (JAKs) enzymes are a family of cytosolic tyrosine kinases that are associated with membrane receptors and play a critical role in the rapid transduction of signals from cell surface to the nucleus. There are four different tyrosine kinases (Tyk2, Jak1, Jak2, Jak3) that share significant structural homology with each other. Binding of cytokines or growth factors to their cognate receptor activate JAK kinases, which in turn mediate the subsequent tyrosine phosphorylation of STAT proteins. Phosphorylated STAT proteins form dimers, translocate to the nucleus, and bind to specific DNA elements to induce or modulate expression of target genes. Aberrant activation of JAK kinases has been implicated in many hematological malignancies and carcinomas. There is also accumulating evidence that constitutive activation of different Jaks and Stats mediate neoplastic transformation and promote abnormal cell proliferation in various malignancies. This review will discuss the role of various Jak-kinase dependent signal transduction pathways in malignancies as well as therapeutic implications of the recent advances in the field.
Keywords: Janus kinase, signal transducer and activator of transcription, suppressors of cytokine signaling, cytokines, signal transduction pathways
Current Enzyme Inhibition
Title: JAK Family of Tyrosine Kinases: Its Functions and Alterations in Human Cancer
Volume: 2 Issue: 2
Author(s): Shahab Uddin, Azhar R. Hussain and Khawla S. Al-Kuraya
Affiliation:
Keywords: Janus kinase, signal transducer and activator of transcription, suppressors of cytokine signaling, cytokines, signal transduction pathways
Abstract: The Janus kinases (JAKs) enzymes are a family of cytosolic tyrosine kinases that are associated with membrane receptors and play a critical role in the rapid transduction of signals from cell surface to the nucleus. There are four different tyrosine kinases (Tyk2, Jak1, Jak2, Jak3) that share significant structural homology with each other. Binding of cytokines or growth factors to their cognate receptor activate JAK kinases, which in turn mediate the subsequent tyrosine phosphorylation of STAT proteins. Phosphorylated STAT proteins form dimers, translocate to the nucleus, and bind to specific DNA elements to induce or modulate expression of target genes. Aberrant activation of JAK kinases has been implicated in many hematological malignancies and carcinomas. There is also accumulating evidence that constitutive activation of different Jaks and Stats mediate neoplastic transformation and promote abnormal cell proliferation in various malignancies. This review will discuss the role of various Jak-kinase dependent signal transduction pathways in malignancies as well as therapeutic implications of the recent advances in the field.
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Cite this article as:
Uddin Shahab, Hussain R. Azhar and Al-Kuraya S. Khawla, JAK Family of Tyrosine Kinases: Its Functions and Alterations in Human Cancer, Current Enzyme Inhibition 2006; 2 (2) . https://dx.doi.org/10.2174/157340806776818766
DOI https://dx.doi.org/10.2174/157340806776818766 |
Print ISSN 1573-4080 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6662 |
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