{"entity":{"id":"paper-darnell-jak-stat-science-1994","kind":"paper","name":"Darnell, Kerr and Stark 1994: JAK-STAT pathways and transcriptional activation by interferons","aka":[],"tldr":"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.","summary":"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.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1126/science.8197455"}],"tags":[],"related":["paper-grivennikov-immunity-inflammation-cancer-cell-2010"],"cancers":[],"sections":[],"technologies":[],"targets":["jak2","ifnar1"],"drugs":[],"companies":[],"institutions":[],"pathways":["jak-stat"],"terms":["cytokine","signalling-pathway"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Science","year":1994,"doi":"10.1126/science.8197455","authors":"Darnell JE Jr, Kerr IM, Stark GR.","paperType":"review","findings":["Interferon receptors activate JAK kinases, which phosphorylate STAT transcription factors that move directly to the nucleus.","Different cytokines use distinct combinations of the JAK and STAT family members.","The pathway provides a rapid, direct route from cell surface to gene activation."],"whatItMeans":"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.","caveats":["A review from the pathway's early days; negative regulators such as SOCS proteins were described later.","Focused on interferons; oncogenic JAK2 mutations were discovered in 2005."],"changedPractice":false},"route":"/key-papers/paper-darnell-jak-stat-science-1994/","neighbours":{"paper":[{"id":"paper-grivennikov-immunity-inflammation-cancer-cell-2010","kind":"paper","name":"Grivennikov, Greten and Karin 2010: immunity, inflammation and cancer","route":"/key-papers/paper-grivennikov-immunity-inflammation-cancer-cell-2010/"}],"target":[{"id":"ifnar1","kind":"target","name":"Interferon alpha receptor (IFNAR1)","route":"/targets/ifnar1/"},{"id":"jak2","kind":"target","name":"JAK2","route":"/targets/jak2/"}],"pathway":[{"id":"jak-stat","kind":"pathway","name":"JAK-STAT signalling","route":"/pathways/jak-stat/"}],"term":[{"id":"cytokine","kind":"term","name":"Cytokine","route":"/terms/cytokine/"},{"id":"signalling-pathway","kind":"term","name":"Signalling pathway","route":"/terms/signalling-pathway/"}]}}