title: 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.
abstract: 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.
authors.affiliation: Hormel Institute, University of Minnesota, Austin, MN 55912, USA.
authors.forename: Tatyana A
authors.initials: TA
authors.lastname: Zykova
authors.forename: Yiguo
authors.initials: Y
authors.lastname: Zhang
authors.forename: Feng
authors.initials: F
authors.lastname: Zhu
authors.forename: Ann M
authors.initials: AM
authors.lastname: Bode
authors.forename: Zigang
authors.initials: Z
authors.lastname: Dong
mesh_terms: D000818:Animals; D044946:Biflavonoids / Q000737:chemistry / Q000494:pharmacology; D002392:Catechin / Q000737:chemistry / Q000494:pharmacology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects / Q000528:radiation effects; D059808:Polyphenols; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D050794:STAT1 Transcription Factor; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D013662:Tea / Q000737:chemistry; D015534:Trans-Activators / Q000378:metabolism*; D014466:Ultraviolet Rays / Q000009:adverse effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D044946:Biflavonoids; D002392:Catechin; D004268:DNA-Binding Proteins; D005419:Flavonoids; D019950:Mitogen-Activated Protein Kinase 1; D010636:Phenols; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D059808:Polyphenols; D047428:Protein Kinase Inhibitors; D050794:STAT1 Transcription Factor; D012694:Serine; D013662:Tea; D015534:Trans-Activators; D048051:p38 Mitogen-Activated Protein Kinases; C494080:Stat1 protein, mouse; C056068:theaflavin