ArticleThe EMBO journal1999
Protein tyrosine kinase Pyk2 mediates the Jak-dependent activation of MAPK and Stat1 in IFN-gamma, but not IFN-alpha, signaling.
Article in The EMBO journal, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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39 citing papers in PubMed, 1 synthesis or guideline pooled it, 130 citations in OpenAlex.
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- JAK2 tyrosine kinase phosphorylates and is negatively regulated by centrosomal protein Ninein.Molecular and cellular biology · 2015Article
- Israeli acute paralysis virus: epidemiology, pathogenesis and implications for honey bee health.PLoS pathogens · 2014Article
- Induction of TRIM22 by IFN-γ Involves JAK and PC-PLC/PKC, but Not MAPKs and pI3K/Akt/mTOR Pathways.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2013Article
- Epithelial to mesenchymal transition promotes breast cancer progression via a fibronectin-dependent STAT3 signaling pathway.The Journal of biological chemistry · 2013Article
- IFN-γ elicits macrophage autophagy via the p38 MAPK signaling pathway.Journal of immunology (Baltimore, Md. : 1950) · 2012Article
- Promyelocytic leukemia protein (PML) regulates endothelial cell network formation and migration in response to tumor necrosis factor α (TNFα) and interferon α (IFNα).The Journal of biological chemistry · 2012Article
- Role of STAT1 in the breast.JAK-STAT · 2012Article
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Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Two distinct types of interferon, IFN-alpha/beta and IFN-gamma, commonly exhibit antiviral activities by transmitting signals to the interior of the cell via their homologous receptors. Receptor stimulation results in the activation of distinct combinations of Janus family protein tyrosine kinases (Jak PTKs); Jak1/Tyk2 and Jak1/Jak2 for IFN-alpha/beta and IFN-gamma, respectively. Jak PTK activation by these IFNs is commonly followed by tyrosine phosphorylation of the transcription factor Stat1 at Y701, which is essential for dimerization, translocation to the nucleus and DNA-binding activity. To gain full transcriptional activity, Stat1 also requires serine phosphorylation at S727. In this paper we demonstrate that Pyk2, which belongs to another PTK family, is critical for the Jak-mediated MAPK and Stat1 activation by IFN-gamma, but not IFN-alpha. Pyk2 is selectively associated with Jak2 and activated by IFN-gamma. Overexpression of PKM, a dominant interfering form of Pyk2, in NIH 3T3 cells results in a strong inhibition of the IFN-gamma-induced activation of Erk2, serine phosphorylation of Stat1 and Stat1-dependent gene transcription. Finally, the antiviral action of IFN-gamma, but not IFN-alpha, is severely impaired by PKM overexpression. Thus, the two types of IFN may utilize distinct Jak-mediated Erk2, and possibly other MAPK activation pathways for their antiviral action.
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