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 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.
Aringer
M
M
Lymphocyte Biology Section, Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892-1820, USA.
Cheng
A
A
Nelson
J W
JW
Chen
M
M
Sudarshan
C
C
Zhou
Y J
YJ
O'Shea
J J
JJ
D000818:Animals; D016207:Cytokines / Q000502:physiology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000378:metabolism; D006128:Growth / Q000502:physiology*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D015394:Molecular Structure; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000235:genetics; D016511:Severe Combined Immunodeficiency / Q000201:enzymology / Q000235:genetics; D015398:Signal Transduction
D016207:Cytokines; D004791:Enzyme Inhibitors; D011993:Recombinant Fusion Proteins; D011505:Protein-Tyrosine Kinases