The protein tyrosine kinase JAK1 complements defects in interferon-α/β and -γ signal transduction

Müller, Mathias; Briscoe, James; Laxton, Carl; Guschin, Dmitry; Ziemiecki, Andrew; Silvennoinen, Olli; Harpur, Ailsa G.; Barbieri, Giovanna; Witthuhn, Bruce A.; Schindler, Christian; Pellegrini, Sandra; Wilks, Andrew F.; Ihle, James N.; Stark, George R.; Kerr, lan M.

doi:10.1038/366129a0

Cited by 733 publications

(429 citation statements)

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“…JAK belongs to a family protein tyrosine kinases that are activators of STAT proteins [7][8][9]. STAT proteins can interact with the receptor/tyrosine kinase complex through its SH2 domain [10][11][12].…”

Section: The Stat Signaling Pathwaymentioning

confidence: 99%

STAT3 in immune responses and inflammatory bowel diseases

2006

Cell Res

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214npg STAT3 has been known as a mediator for gene expression induced by many important cytokines. Recent studies have suggested that STAT3 has important functions in regulation of both innate and adaptive immunity. Loss of STAT3 in immune cells caused severe inflammation in response to pathogens. This review discusses the recent progress and suggests directions for the future research on this interesting molecule.

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Section: The Stat Signaling Pathwaymentioning

confidence: 99%

STAT3 in immune responses and inflammatory bowel diseases

2006

Cell Res

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“…Through studies in mutant cell lines lacking individual JAK family members it was established that individual JAKs are dispensable for growth factor mediated STAT activation (Leaman et al, 1996;Vignais et al, 1996). This is in contrast to cytokine signaling where usually at least one JAK is essential for STAT activation (MuÈ ller et al, 1993). Thus for growth factor signaling, either JAKs are not involved or are redundant.…”

Section: Introductionmentioning

confidence: 99%

STAT activation by the PDGF receptor requires juxtamembrane phosphorylation sites but not Src tyrosine kinase activation

1999

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Activation of the platelet-derived growth factor (PDGF) receptor tyrosine kinase induces tyrosine phosphorylation of Signal Transducer and Activator of Transcription (STAT) proteins. Since the PDGF receptor also activates the Src tyrosine kinase, it is possible that Src mediates tyrosine phosphorylation of STATs in PDGFtreated cells. Consistent with a role for Src in STAT activation, we found that a PDGF receptor juxtamembrane tyrosine residue required for Src activation is necessary and su cient for activation of STATs 1 and 3. To test the Src requirement further, we made other mutations in the PDGF receptor juxtamembrane region that increased or decreased Src binding. In epithelial and ®broblast cells, PDGF activated STAT1, 3 and 6 in the absence of detectable binding and activation of Src. In addition, PDGF induced c-myc RNA expression and DNA synthesis even though Src was not detectably activated. The activation of MAP kinase and the induction of c-fos gene expression both correlated with STAT but not Src activation by the receptor. We conclude that juxtamembrane tyrosine phosphorylation is necessary for both Src tyrosine kinase and STAT activation by the bPDGF receptor, but that both processes are regulated independently by this region.

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“…Although we failed to clone the CaJAK1 gene, homologs have been identified in other fish species [36,37]. Furthermore, the fact that CaJAK1 and CaSTAT1 transcription were activated at the same time in IFN-induced CAB cells suggested that CaJAK1 was also likely to participate in STAT1-catalyzed phosphorylation events, as with human JAK1 [2,56]. From the same cell system CaIRF7 was also cloned and could be activated by CAB IFN [27], hinting that fish IRF7 may function as mammalian IRF7 to participate in the IFN signaling cascade.…”

Section: Discussionmentioning

confidence: 93%