Involvement of Hgs/Hrs in signaling for cytokine-mediated c-fos induction through interaction with TAK1 and Pak1.
Hgs/Hrs is a tyrosine-phosphorylated FYVE finger protein that is induced by stimulation with various cytokines and growth factors. Here we show that Hgs plays critical roles in the signaling pathway for the interleukin-2-induced activation of the serum-response element and cyclic AMP-response element of the c-fos promoter. We found that Hgs associated physically with transforming growth factor-beta-activated kinase 1 (TAK1) and p21-activated kinase 1 (Pak1), which mediate the activation of c-Jun N-terminal kinase and serum response factor, respectively, leading to transactivation via the serum-response element and cyclic AMP-response element. These results suggest that Hgs is involved in the TAK1-JNK and Pak1-serum response factor pathways for the c-fos induction that is initiated by cytokines.
Sasaki
Y
Y
Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine and CREST Program of the Japan Science, and Technology Corporation, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Sugamura
K
K
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation; D005799:Genes, Dominant; D017930:Genes, Reporter; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007376:Interleukin-2 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases; D008156:Luciferases / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D026362:Serum Response Factor; D015398:Signal Transduction; D013997:Time Factors; D015533:Transcriptional Activation; D014443:Tyrosine / Q000378:metabolism; D054462:p21-Activated Kinases; D000099151:MAP Kinase Kinase Kinase 7
D016207:Cytokines; D004268:DNA-Binding Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007376:Interleukin-2; D048031:JNK Mitogen-Activated Protein Kinases; D008156:Luciferases; D020930:MAP Kinase Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D016760:Proto-Oncogene Proteins c-fos; D026362:Serum Response Factor; D014443:Tyrosine; D054462:p21-Activated Kinases; D000099151:MAP Kinase Kinase Kinase 7; C515903:PAK1 protein, human; C515905:Pak1 protein, mouse