Journal Article

The signal transduction networks required for phosphorylation of STAT1 at Ser727 in mouse epidermal JB6 cells in the UVB response and inhibitory mechanisms of tea polyphenols

Tatyana A. Zykova, Yiguo Zhang, Feng Zhu, Ann M. Bode and Zigang Dong

in Carcinogenesis

Volume 26, issue 2, pages 331-342
Published in print February 2005 | ISSN: 0143-3334
Published online February 2005 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgh334
The signal transduction networks required for phosphorylation of STAT1 at Ser727 in mouse epidermal JB6 cells in the UVB response and inhibitory mechanisms of tea polyphenols

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Signal transducers and activators of transcription (STATs) play a critical role in signal transduction pathways. STATs are a family of cytoplasmic proteins with roles as signal messengers and transcription factors that participate in normal cellular responses to cytokines and growth factors. Phosphorylation of STAT1 at Ser727 is essential for its activation and occurs in response to stress signals, inflammation or infection. We observed that UVB induced phosphorylation of STAT1 (Ser727) in mouse epidermal JB6 Cl41 cells. This stimulation was inhibited by PD98059 and UO126, wortmannin, LY294002, SB202190 and SP600125 and dominant negative mutants of ERK2 (DNM-ERK2), p38 (DNM-p38) and JNK1 (DNM-JNK1). The response was absent in Jnk1−/− or Jnk2−/− knockout cells, but was unaffected by a dominant negative mutant of the phosphatidylinositol-3 kinase (PI-3K) p85 subunit (DNM-Δp85). STAT1 (Ser727) phosphorylation was also blocked in a Rsk2 cell line. In Pdk1−/− cells STAT1 was not activated by UVB stimulation compared with strong activation in Pdk1+/+ cells. Our data indicate that phosphorylation of STAT1 (Ser727) occurs through PI-3K, ERKs, p38 kinase, JNKs, PDK1 and p90RSK2 in the cellular response to UVB. We also show an inhibitory effect of theaflavins and EGCG on UVB-induced STAT1 (Ser727), ERKs, JNKs, PDK1 and p90RSK2 phosphorylation.

Keywords: AP-1, activator protein-1; DMEM, Dulbecco's modified Eagle's medium; DNM, dominant negative mutants; EGCG, (−)-epigallocatechin 3-gallate; EGF, epidermal growth factor; EMEM, Eagle's minimum essential medium; ERKs, extracellular signal-regulated kinases; FBS, fetal bovine serum; GST, glutathione S-transferase; IFN, type I interferon; JNKs, c-Jun N-terminal kinases; MAPK, mitogen-activated protein kinase; MEK, MAPK/ERK kinase; MSK1, mitogen- and stress-activated protein kinase 1; NP, non-phosphorylated; p90RSK, p90 kDa ribosomal S6 kinases; PBS, phosphate-buffered saline; PDK1, phosphoinositide-dependent protein kinase 1; PI-3K, phosphatidylinositol-3 kinase; PMSF, phenylmethylsulfonyl fluoride; STATs, signal transducers and activators of transcription; TPA, 12-O-tetradecanoyl-phorbol-13-acetate

Journal Article.  8467 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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