Establishment of molecular basis on ligand recognition by the insect prothoracicotropic hormone receptor

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K14720
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Bioorganic chemistry
• Research Institution: Himeji Dokkyo University (2016); The University of Tokyo (2015)
• Principal Investigator: SAITO Kazuki 姫路獨協大学, 薬学部, 教授 (10192585)
• Co-Investigator(Renkei-kenkyūsha): KATAOKA Hiroshi 東京大学, 大学院新領域創成科学研究科, 教授 (60202008)
• Research Collaborator: KONOGAMI Tadafumi ; YAMASHITA Yusuke
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 前胸腺刺激ホルモン（PTTH） / Torso / チロシンキナーゼ型レセプター / ジスルフィド架橋によるレセプター二量化 / カイコガ / 自己リン酸化 / 下流ERKリン酸化の促進

Outline of Final Research Achievements

Insect prothoracicotropic hormone (PTTH) receptor, Torso, is a member of the receptor-tyrosine-kinase family. In this study, we detected ligand-independent dimerization of silkworm Torso, and found that the receptor molecules in the dimer were linked by intermolecular disulfide bridges in the transmembrane region. When all of the cysteines in the region were replaced with phenylalanines, non-covalent dimerization of the mutant was detected using a cross-linking reagent, both with and without ligand stimulation. This non-covalent dimerization caused apparent receptor autophosphorylation independently of the ligand stimulation, but did not promote the ERK phosphorylation in the downstream signaling pathway. The intermolecular disulfide bridges in the transmembrane region may play a key role in an activation process of the receptor, Torso.

Free Research Field

分子認識化学