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The review that defined the JAK-STAT pathway, the direct route by which interferons and many other cytokines tell a cell's genes to respond, and which is now the target of JAK inhibitors used in blood cancers.
Darnell, Kerr and Stark drew together the genetics and biochemistry that revealed how interferons signal: receptor binding activates Janus kinases (JAKs), which phosphorylate STAT proteins that dimerise, move to the nucleus and switch on genes within minutes. They showed that the same JAK-STAT logic is shared by many cytokines and growth factors, each using a particular combination of JAKs and STATs. The paper gave the pathway its name and set out the model that has held since.
The JAK-STAT pathway explains how interferon and interleukin signals act in immunity and cancer. Its discovery underlies ruxolitinib and other JAK inhibitors in myeloproliferative neoplasms, the role of STAT3 in tumour-promoting inflammation, and the interferon-gamma signalling that determines whether tumours respond to checkpoint inhibitors.
Shares JAK-STAT signalling, JAK2.
Shares Grivennikov, Greten and Karin 2010: immunity, inflammation and cancer, JAK-STAT signalling.
Shares Cytokine, Signalling pathway.
Shares JAK-STAT signalling, JAK2.
Shares JAK-STAT signalling, JAK2.
Shares JAK-STAT signalling, JAK2.
Shares Grivennikov, Greten and Karin 2010: immunity, inflammation and cancer, Cytokine.
Shares JAK-STAT signalling, JAK2.