PMID- 18835249 OWN - NLM STAT- MEDLINE DCOM- 20081215 LR - 20191210 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 377 IP - 3 DP - 2008 Dec 19 TI - Differential subcellular localization of insulin receptor substrates depends on C-terminal regions and importin beta. PG - 741-6 LID - 10.1016/j.bbrc.2008.09.106 [doi] AB - Insulin receptor substrates (IRSs) play essential roles in signal transduction of insulin and insulin-like growth factors. Previously, we showed that IRS-3 is localized to the nucleus as well as the cytosol, while IRS-1 and 2 are mainly localized to the cytoplasm. In the present study, we found that importin beta directly interacts with IRS-3 and is able to mediate nuclear transport of IRS-3. Importin beta interacted with the pleckstrin homology domain, the phosphotyrosine binding domain and the C-terminal region of IRS-3; indeed all of these fragments exhibited predominant nuclear localization. By contrast, almost no interaction of importin beta with IRS-1 and -2 was observed, and their C-terminal regions displayed discrete spotty images in the cytosol. In addition, using chimeric proteins between IRS-1 and IRS-3, we revealed that the C-terminal regions are the main determinants of the differing subcellular localizations of IRS-1 and IRS-3. FAU - Kabuta, Tomohiro AU - Kabuta T AD - Laboratory of Cell Regulation, Departments of Animal Sciences and Applied Biological Chemistry, Graduate School of Agriculture and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan. FAU - Take, Kazumi AU - Take K FAU - Kabuta, Chihana AU - Kabuta C FAU - Hakuno, Fumihiko AU - Hakuno F FAU - Takahashi, Shin-ichiro AU - Takahashi S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20081001 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (beta Karyopherins) RN - 21820-51-9 (Phosphotyrosine) RN - EC 2.7.10.1 (Receptor, Insulin) SB - IM MH - Animals MH - COS Cells MH - Cell Nucleus/metabolism MH - Chlorocebus aethiops MH - Cytosol/metabolism MH - Humans MH - Mutation MH - Phosphotyrosine/metabolism MH - Protein Structure, Tertiary MH - Rats MH - Receptor, Insulin/genetics/*metabolism MH - beta Karyopherins/genetics/*metabolism EDAT- 2008/10/07 09:00 MHDA- 2008/12/17 09:00 CRDT- 2008/10/07 09:00 PHST- 2008/09/24 00:00 [received] PHST- 2008/09/25 00:00 [accepted] PHST- 2008/10/07 09:00 [pubmed] PHST- 2008/12/17 09:00 [medline] PHST- 2008/10/07 09:00 [entrez] AID - S0006-291X(08)01890-1 [pii] AID - 10.1016/j.bbrc.2008.09.106 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2008 Dec 19;377(3):741-6. doi: 10.1016/j.bbrc.2008.09.106. Epub 2008 Oct 1.