Janus kinases and their role in growth and disease

Janus kinases (JAK) play a crucial role in the initial steps of cytokine signaling. Each of the four members (JAK1, JAK2, JAK3, TYK2) of this non-receptor tyrosine kinase family is indispensable for the effects of distinct cytokines. Moreover, recent reports have added to our knowledge on their high...

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Bibliographic Details
Published in:Life Sciences 1999, Vol.64 (24), p.2173-2186
Main Authors: Aringer, M., Cheng, A., Nelson, J.W., Chen, M., Sudarshan, C., Zhou, Y.-J., O'Shea, J.J.
Format: Article
Language:English
Subjects:
Animals
cytokine receptors
Cytokines - physiology
Enzyme Activation
Enzyme Inhibitors - metabolism
Growth - physiology
Humans
interferons
interleukins
Janus kinases
Mice
Mice, Knockout
Molecular Structure
Neoplasms - enzymology
Neoplasms - genetics
Protein-Tyrosine Kinases - antagonists & inhibitors
Protein-Tyrosine Kinases - genetics
Protein-Tyrosine Kinases - physiology
Recombinant Fusion Proteins - genetics
Severe Combined Immunodeficiency - enzymology
Severe Combined Immunodeficiency - genetics
Signal Transduction
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Summary:Janus kinases (JAK) play a crucial role in the initial steps of cytokine signaling. Each of the four members (JAK1, JAK2, JAK3, TYK2) of this non-receptor tyrosine kinase family is indispensable for the effects of distinct cytokines. Moreover, recent reports have added to our knowledge on their highly specific functions: JAK3 knockout mice and JAK3 deficient patients cannot signal through the interleukin-2,4,7,9, or 15 receptors and suffer from severe combined immunodeficiency (SCID). JAK1 and JAK2 knockout mice do not survive, their cells again showing distinct patterns of cytokine signaling deficits. At the other end of the spectrum, JAK fusion proteins have been shown to play a role in leukemias. In addition, a new class of JAK-specific inhibitors was described by several groups, the CIS/SOCS/Jab family. This review on the rapidly growing field focuses on JAK function and regulation, and on their emerging role in development and human disease.
ISSN:0024-3205
1879-0631
DOI:10.1016/S0024-3205(98)00538-4