TY - JOUR
T1 - 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 polypyhenols
AU - Zykova, Tatiana
AU - Zhang, Yiguo
AU - Zhu, Feng
AU - Bode, Ann M.
AU - Dong, Zigang
N1 - Funding Information:
This work was supported by The Hormel Foundation and National Institutes of Health grants CA81064 and CA77646.
PY - 2005/2
Y1 - 2005/2
N2 - 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 U0126, 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.
AB - 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 U0126, 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.
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U2 - 10.1093/carcin/bgh334
DO - 10.1093/carcin/bgh334
M3 - Article
C2 - 15550455
AN - SCOPUS:13844275388
SN - 0143-3334
VL - 26
SP - 331
EP - 342
JO - Carcinogenesis
JF - Carcinogenesis
IS - 2
ER -