Role of Per1-interacting protein of the suprachiasmatic nucleus in NGF mediated neuronal survival.
We previously identified Per1-interacting protein of the suprachiasmatic nucleus (PIPS) in rats. To reveal its role, its tissue distribution was examined by immunoblotting. PIPS-like immunoreactive substance (PIPSLS) was observed in the brain, adrenal gland, and PC12 cells. Since PIPS, which has no nuclear localization signal (NLS), is translocated into nuclei of COS-7 cells in the presence of mPer1, the effect of NGF on nuclear localization of PIPS was examined using PC12 cells. NGF caused nuclear translocation of either PIPSLS or GFP-PIPS. NGF mediated nuclear translocation of PIPSLS was blocked by K252a, a TrkA-inhibitor, or wortmannin, a PI3K-inhibitor. Gab1, which is implicated in TrkA signaling and has NLS, co-immunoprecipitated with PIPSLS from PC12 cells using an anti-PIPS antibody. Inhibition of PIPS expression by RNAi increased levels of apoptosis in PC12 cells. These findings suggest that nuclear translocation of PIPS is involved in NGF mediated neuronal survival via TrkA, PI3K, and Gab1 signaling pathway.
Kiyama
Atsuko
A
Institute for Protein Research, Osaka University, 3-2 Yamada-Oka, Suita, Osaka 565-0871, Japan. kiyama@pu-hiroshima.ac.jp
Isojima
Yasushi
Y
Nagai
Katsuya
K
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D005786:Gene Expression Regulation; D008297:Male; D020932:Nerve Growth Factor / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D009928:Organ Specificity; D016716:PC12 Cells; D010750:Phosphoproteins / Q000378:metabolism; D011485:Protein Binding; D034622:RNA Interference; D051381:Rats; D017208:Rats, Wistar; D020917:Receptor, trkA / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013493:Suprachiasmatic Nucleus / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D000077191:Wortmannin
D000730:Androstadienes; C490896:Gab1 protein, rat; C443439:Gprasp1 protein, rat; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D020932:Nerve Growth Factor; D020917:Receptor, trkA; D000077191:Wortmannin