Zykova Tatyana A, Zhang Yiguo, Zhu Feng, Bode Ann M, Dong Zigang
Hormel Institute, University of Minnesota, Austin, MN 55912, USA.
Carcinogenesis. 2005 Feb;26(2):331-42. doi: 10.1093/carcin/bgh334. Epub 2004 Nov 18.
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-Deltap85). 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.
信号转导子和转录激活子（STATs）在信号转导通路中发挥着关键作用。STATs是一类细胞质蛋白，作为信号信使和转录因子，参与细胞对细胞因子和生长因子的正常应答。STAT1在Ser727位点的磷酸化对其激活至关重要，且在应激信号、炎症或感染反应中发生。我们观察到，紫外线B（UVB）可诱导小鼠表皮JB6 Cl41细胞中STAT1（Ser727）的磷酸化。这种刺激被PD98059、UO126、渥曼青霉素、LY294002、SB202190、SP600125以及ERK2（DNM-ERK2）、p38（DNM-p38）和JNK1（DNM-JNK1）的显性负性突变体所抑制。在Jnk1（-/-）或Jnk2（-/-）基因敲除细胞中未出现该反应，但不受磷脂酰肌醇-3激酶（PI-3K）p85亚基（DNM-Δp85）的显性负性突变体影响。在Rsk2（-）细胞系中，STAT1（Ser727）的磷酸化也被阻断。与Pdk1（+/+）细胞中的强烈激活相比，在Pdk1（-/-）细胞中，UVB刺激未激活STAT1。我们的数据表明，在细胞对UVB的应答中，STAT1（Ser727）的磷酸化通过PI-3K、ERK、p38激酶、JNK、PDK1和p90RSK2发生。我们还显示了茶黄素和表没食子儿茶素没食子酸酯（EGCG）对UVB诱导的STAT1（Ser727）、ERK、JNK、PDK1和p90RSK2磷酸化的抑制作用。
