2000
DOI: 10.1074/jbc.c000129200
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A Gain-of-function Mutation in STAT6

Abstract: Interleukin-4 (IL-4) is a cytokine that plays a crucial role in the pathophysiology of asthma and allergic diseases. IL-4-induced gene expression is largely mediated through the activation of the latent transcription factor STAT6. We identified a STAT6 mutant (STAT6VT)) that is activated independently of IL-4 stimulation. STAT6VT carries two amino acid changes in the SH2 domain that affect the overall structure and stability of the monomeric and dimeric protein. When overexpressed in mammalian cells, STAT6VT u… Show more

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Cited by 61 publications
(62 citation statements)
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References 47 publications
(54 reference statements)
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“…In STAT6VT transfectants, immunoprecipitation experiments revealed a constitutive tyrosine phosphorylation of STAT6 (Figure 7a lower panel), as previously described in other cell lines (Daniel et al, 2000). Subsequently, the transcriptional potential of STAT6VT was assessed using an IL-4 inducible luciferase reporter construct carrying ®ve copies of Figure 6 E ect of pharmacological inhibitors on IL-4/IL-13-induced IL-13Ra2 expression.…”
Section: Il-4 and Il-13 Signal Transduction In Keratinocytessupporting
confidence: 64%
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“…In STAT6VT transfectants, immunoprecipitation experiments revealed a constitutive tyrosine phosphorylation of STAT6 (Figure 7a lower panel), as previously described in other cell lines (Daniel et al, 2000). Subsequently, the transcriptional potential of STAT6VT was assessed using an IL-4 inducible luciferase reporter construct carrying ®ve copies of Figure 6 E ect of pharmacological inhibitors on IL-4/IL-13-induced IL-13Ra2 expression.…”
Section: Il-4 and Il-13 Signal Transduction In Keratinocytessupporting
confidence: 64%
“…Whether STAT6 is implicated in IL-13Ra2 induction was assessed using a gain-of-function mutant of STAT6 (Daniel et al, 2000). This constitutive active mutant, STAT6VT, was not su cient alone to induce IL-13Ra2 mRNA expression, but strongly potentiated the induction triggered by IL-4 and IL-13.…”
Section: Discussionmentioning
confidence: 99%
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“…We used the three key transcription factors that are essential for osteoclastic TRAP expression, NFATc1, PU.1, and MITF (8,11), and STAT6VT, a constitutively active form of STAT6 (42). The combination of NFATc1, PU.1, and MITF has been shown to induce TRAP transcription in the absence of RANKL treatment (8,11); STAT6VT can bind to the STAT6-responsive element and regulate transcription without IL-4 treatment (42). Various combinations of these transcription factors were transfected into RAW264.7 cells.…”
Section: Il-4 Suppresses the Rankl-induced Trap Expression By Inhibitmentioning
confidence: 99%
“…Though necessary for this signaling event, we have not determined whether Stat6 activation alone is sufficient to decrease IgE receptor expression. To this end, we infected Stat6-deficient BMMC populations with a retrovirus expressing constitutively active Stat6 (Stat6VT) (32) and GFP or with a control retrovirus expressing GFP alone. As shown in Fig.…”
Section: Role Of Stat6 In Fc⑀ri Down-regulationmentioning
confidence: 99%