Functional regulation of TEL by p38-induced phosphorylation.
TEL is a nuclear phosphoprotein that belongs to a member of the ETS family transcription factors. TEL acts as a tumor suppressor and is essential for establishing hematopoiesis in neonatal bone marrow. Because TEL possesses multiple putative mitogen-activated protein (MAP) kinase phosphorylation sites, we here investigated functional regulation of TEL via stress signaling pathways. We showed that TEL becomes phosphorylated in vivo by activated p38 but not by JNK1. The constitutive and inducible phosphorylation sites were found to be Ser(22) and Ser(257), respectively. TEL bound to p38 and was directly phosphorylated in vitro by p38. In vivo p38-dependent phosphorylation reduced trans-repressional abilities of TEL through ETS-binding consensus site. These data indicate that TEL's functions are potentially regulated by p38 which is activated by various kinds of stresses. TEL could be a constituent downstream of the specific MAP kinase in the signal transduction system.
Arai
Honoka
H
Department of Hematology, Dokkyo University School of Medicine, 321-0293, Tochigi, Japan.
Maki
Kazuhiro
K
Waga
Kazuo
K
Sasaki
Ko
K
Nakamura
Yuichi
Y
Imai
Yoichi
Y
Kurokawa
Mineo
M
Hirai
Hisamaru
H
Mitani
Kinuko
K
D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics*; D017353:Gene Deletion; D005786:Gene Expression Regulation; D005982:Glutathione Transferase / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009154:Mutation; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics*; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases; D000097764:ETS Translocation Variant 6 Protein
D004268:DNA-Binding Proteins; D005982:Glutathione Transferase; D008156:Luciferases; D020928:Mitogen-Activated Protein Kinases; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D012694:Serine; D048051:p38 Mitogen-Activated Protein Kinases; D000097764:ETS Translocation Variant 6 Protein