STAT6 phosphorylation inhibitors block eotaxin-3 secretion in bronchial epithelial cells.
The STAT6 (signal transducer and activator of transcription 6) protein facilitates T-helper cell 2 (Th2) mediated responses that control IgE-mediated atopic diseases such as asthma. We have identified compounds that bind to STAT6 and inhibit STAT6 tyrosine phosphorylation induced by IL-4. In the bronchial epithelial cell line BEAS-2B, compound (R)-84 inhibits the secretion of eotaxin-3, a chemokine eliciting eosinophil infiltration. (R)-84 appears to prevent STAT6 from assuming the active dimer configuration by directly binding the protein and inhibiting tyrosine phosphorylation.
Center for Computational and Integrative Biology, Massachusetts General Hospital, 185 Cambridge St., Boston, MA 02114, USA.
Li
L
Zhou
Tomohiko
T
Kawate
Xiaorong
X
Liu
Young Bae
YB
Kim
Yajuan
Y
Zhao
Guohong
G
Feng
Julian
J
Banerji
Huw
H
Nash
Charles
C
Whitehurst
Satish
S
Jindal
Arshad
A
Siddiqui
Brian
B
Seed
Jia L
JL
Wolfe
D002460:Cell Line; D000075906:Chemokine CCL26; D019742:Chemokines, CC / Q000378:metabolism*; D019281:Dimerization; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D010766:Phosphorylation; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D019948:Receptors, Interleukin-4 / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013237:Stereoisomerism
C120429:CCL26 protein, human; D000075906:Chemokine CCL26; D019742:Chemokines, CC; D007211:Indoles; D011725:Pyridines; D019948:Receptors, Interleukin-4; D050800:STAT6 Transcription Factor; D015847:Interleukin-4