Regulation of ultraviolet B-induced phosphorylation of histone H3 at serine 10 by Fyn kinase.
Ultraviolet B (UVB) induces phosphorylation of histone H3 at serine 10, and mitogen-activated protein kinases are involved in this signal transduction pathway. Here we provide evidence that Fyn kinase, a member of the Src kinase family, is involved in the UVB-induced phosphorylation of histone H3 at serine 10. UVB distinctly increased Fyn kinase activity and phosphorylation. Fyn kinase inhibitors 4-amino-5-(4-chlorophenyl)-7(t-butyl)pyrazol(3,4-d)pyramide and leflunomide, an Src kinase inhibitor, suppressed both UVB-induced phosphorylation of histone H3 at serine 10 and Fyn kinase activity and phosphorylation. UVB-induced phosphorylation of histone H3 at serine 10 was blocked by either a dominant-negative mutant of Fyn (DNM-Fyn) kinase or small interfering RNA of Fyn kinase. UVB-induced phosphorylation and activities of ERKs and protein kinase B/Akt were markedly inhibited by DNM-Fyn kinase. However, DNM-Fyn kinase did not inhibit UVB-induced phosphorylation of p38 MAPK or c-Jun N-terminal kinases. Active Fyn kinase phosphorylated histone H3 at serine 10 in vitro, and the phosphorylated Fyn kinase could translocate into the nucleus of HaCaT cells. These results indicate that Fyn kinase plays a key role in the UVB-induced phosphorylation of histone H3 at serine 10.
He
Zhiwei
Z
Hormel Institute, University of Minnesota, Austin, Minnesota 55912, USA.
Cho
Yong-Yeon
YY
Ma
Wei-Ya
WY
Choi
Hong Seok
HS
Bode
Ann M
AM
Dong
Zigang
Z
D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005799:Genes, Dominant; D006657:Histones / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007555:Isoxazoles / Q000494:pharmacology; D000077339:Leflunomide; D020935:MAP Kinase Signaling System; D051379:Mice; D008954:Models, Biological; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D051076:Proto-Oncogene Proteins c-fyn; D034741:RNA, Small Interfering / Q000378:metabolism; D012694:Serine / Q000737:chemistry* / Q000378:metabolism; D015398:Signal Transduction; D013912:Threonine / Q000737:chemistry; D013997:Time Factors; D014162:Transfection; D014466:Ultraviolet Rays; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism*
D006657:Histones; D007555:Isoxazoles; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D013912:Threonine; D012694:Serine; C494957:FYN protein, human; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn; D019061:src-Family Kinases; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; D000077339:Leflunomide