Endosomal sorting signal of cytokine receptors and its single nucleotide polymorphism in allergy disease

• Project/Area Number: 25461586
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Shinshu University
• Principal Investigator: TAKESHITA Toshikazu 信州大学, 学術研究院医学系, 教授 (60212023)
• Co-Investigator(Renkei-kenkyūsha): KOJIMA Katsuhiko 信州大学, 学術研究院医学系, 講師 (80345743) ; YOSHINO Kazuhisa 信州大学, 学術研究院医学系, 助教 (40551859) ; AMANO Yuji 信州大学, 学術研究院医学系, 助教 (50624681)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: サイトカイン / サイトカイン受容体 / アレルギー / 受容体遺伝子多型 / 小胞輸送シグナル

Outline of Final Research Achievements

In lymphoid cell, intracellular compartments, which keep the specific substances of the system and exchanges the substances between the compartments, is supported by endosomal sorting. Here, we elucidated endosomal sorting mechanism of interleukin-2 receptor β (IL-2Rβ) and interleukin-4 receptor α (IL-4Rα), and explored single nucleotide polymorphism (SNP) of the receptors in allergy patients. We identified novel SNPs in IL-4Rα gene locus of the patients. On the other hand, the SNP involved in endosomal sorting was not detected in the patients.

Research Products

• [Journal Article] ESCRT-0 protein hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) is targeted to endosomes independently of signal-transducing adaptor molecule (STAM) and the complex formation with STAM promotes its endosomal dissociation (2014)
  • Author(s): Kojima, K., Amano, Y., Yoshino, K., Tanaka, N., Sugamura, K., Takeshita, T.
  • Journal Title: J Biol Chem Volume: 289 Issue: 48 Pages: 33296-33310
  • DOI: 10.1074/jbc.m114.578245
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A hydrophobic amino acid cluster inserted into the C-terminus of a recycling cell surface receptor functions as an endosomal sorting signal (2013)
  • Author(s): Amano Y., Yoshino K., Kojima K., Takeshita T.
  • Journal Title: Biochem Biophys Res Commun Volume: 441 Issue: 1 Pages: 164-168
  • DOI: 10.1016/j.bbrc.2013.10.019
  • Peer Reviewed
• [Presentation] Hydrophobic amino acid cluster in the cytoplasmic tail of interleukin-2 receptor βchain acts as a sorting signal for lysosome
  • Author(s): 天野勇治、その他
  • Organizer: 国際免疫学会
  • Place of Presentation: ミラノ（イタリア）