Article ; Online: JAK/STAT: Why choose a classical or an alternative pathway when you can have both?
Journal of cellular and molecular medicine
2022 Volume 26, Issue 7, Page(s) 1865–1875
Abstract: A subset of cytokines triggers the JAK-STAT pathway to exert various functions such as the induction of inflammation and immune responses. The receptors for these cytokines are dimers/trimers of transmembrane proteins devoid of intracellular kinase ... ...
| Abstract | A subset of cytokines triggers the JAK-STAT pathway to exert various functions such as the induction of inflammation and immune responses. The receptors for these cytokines are dimers/trimers of transmembrane proteins devoid of intracellular kinase activity. Instead, they rely on Janus kinases (JAKs) for signal transduction. Classical JAK-STAT signalling involves phosphorylation of cytokine receptors' intracellular tyrosines, which subsequently serve as docking sites for the recruitment and activation of STATs. However, there is evidence to show that several cytokine receptors also use a noncanonical, receptor tyrosine-independent path to induce activation of STAT proteins. We identified two main alternative modes of STAT activation. The first involves an association between a tyrosine-free region of the cytokine receptor and STATs, while the second seems to depend on a direct interaction between JAK and STAT proteins. We were able to identify the use of noncanonical mechanisms by almost a dozen cytokine receptors, suggesting they have some importance. These alternative pathways and the receptors that employ them are discussed in this review. |
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| MeSH term(s) | Janus Kinases/genetics ; Janus Kinases/metabolism ; Phosphorylation ; Receptors, Cytokine/genetics ; Receptors, Cytokine/metabolism ; STAT Transcription Factors/genetics ; STAT Transcription Factors/metabolism ; Signal Transduction/physiology | |||||
| Chemical Substances | Receptors, Cytokine ; STAT Transcription Factors ; Janus Kinases (EC 2.7.10.2) | |||||
| Language | English | |||||
| Publishing date | 2022-03-03 | |||||
| Publishing country | England | |||||
| Document type | Journal Article ; Review | |||||
| ZDB-ID | 2074559-X | |||||
| ISSN | 1582-4934 ; 1582-4934 ; 1582-1838 | |||||
| ISSN (online) | 1582-4934 | |||||
| ISSN | 1582-4934 ; 1582-1838 | |||||
| DOI | 10.1111/jcmm.17168 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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