The JAK-STAT pathway at 30: Much learned, much more to do

Rachael L. Philips; Yuxin Wang; Hyeon Joo Cheon; Yuka Kanno; Massimo Gadina; Vittorio Sartorelli; Curt M. Horvath; James E. Darnell; George R. Stark; John J. O'Shea

doi:10.1016/j.cell.2022.09.023

The JAK-STAT pathway at 30: Much learned, much more to do

Rachael L. Philips, Yuxin Wang, Hyeon Joo Cheon, Yuka Kanno, Massimo Gadina, Vittorio Sartorelli, Curt M. Horvath, James E. Darnell, George R. Stark, John J. O'Shea^*

^*Corresponding author for this work

Molecular Biosciences

Research output: Contribution to journal › Review article › peer-review

212 Scopus citations

Abstract

The discovery of the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway arose from investigations of how cells respond to interferons (IFNs), revealing a paradigm in cell signaling conserved from slime molds to mammals. These discoveries revealed mechanisms underlying rapid gene expression mediated by a wide variety of extracellular polypeptides including cytokines, interleukins, and related factors. This knowledge has provided numerous insights into human disease, from immune deficiencies to cancer, and was rapidly translated to new drugs for autoimmune, allergic, and infectious diseases, including COVID-19. Despite these advances, major challenges and opportunities remain.

Original language	English (US)
Pages (from-to)	3857-3876
Number of pages	20
Journal	Cell
Volume	185
Issue number	21
DOIs	https://doi.org/10.1016/j.cell.2022.09.023
State	Published - Oct 13 2022

Funding

IFNs were first described over 70 years ago, leading to an extraordinary body of literature. Unfortunately, space limitations preclude including many outstanding citations—our apologies to all whose work could not be cited. This work was supported by the Intramural Research Programs of NIAMS . R.L.P. was supported by a Postdoctoral Research Associate (PRAT) fellowship from the National Institute of General Medical Sciences (NIGMS), award number 1Fi2GM137942-01 . Additionally, Y.W. was supported by the National Heart Lung and Blood Institute (NHLBI), award number R56 HL160639 , and G.R.S. was supported by the National Institute of Allergy and Infectious Diseases (NIAID), award number R01 AI153085 , and the National Cancer Institute (NCI), award number P01CA062220 . H.C. was supported by National Cancer Institute (NCI), award numbers R21CA252387 and R03CA215941 . IFNs were first described over 70 years ago, leading to an extraordinary body of literature. Unfortunately, space limitations preclude including many outstanding citations—our apologies to all whose work could not be cited. This work was supported by the Intramural Research Programs of NIAMS. R.L.P. was supported by a Postdoctoral Research Associate (PRAT) fellowship from the National Institute of General Medical Sciences (NIGMS), award number 1Fi2GM137942-01. Additionally, Y.W. was supported by the National Heart Lung and Blood Institute (NHLBI), award number R56 HL160639, and G.R.S. was supported by the National Institute of Allergy and Infectious Diseases (NIAID), award number R01 AI153085, and the National Cancer Institute (NCI), award number P01CA062220. H.C. was supported by National Cancer Institute (NCI), award numbers R21CA252387 and R03CA215941. The NIH holds a US patent related to JAK inhibitors, and Dr. O'Shea receives royalty income.

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.cell.2022.09.023

Cite this

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title = "The JAK-STAT pathway at 30: Much learned, much more to do",

abstract = "The discovery of the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway arose from investigations of how cells respond to interferons (IFNs), revealing a paradigm in cell signaling conserved from slime molds to mammals. These discoveries revealed mechanisms underlying rapid gene expression mediated by a wide variety of extracellular polypeptides including cytokines, interleukins, and related factors. This knowledge has provided numerous insights into human disease, from immune deficiencies to cancer, and was rapidly translated to new drugs for autoimmune, allergic, and infectious diseases, including COVID-19. Despite these advances, major challenges and opportunities remain.",

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The JAK-STAT pathway at 30: Much learned, much more to do

Abstract

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ASJC Scopus subject areas

UN SDGs

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