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SASH1: A Novel Eph Receptor Partner and Insights into SAM-SAM Interactions.

التفاصيل البيبلوغرافية
العنوان: SASH1: A Novel Eph Receptor Partner and Insights into SAM-SAM Interactions.
المؤلفون: Ding Y; Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen 518036, China. Electronic address: https://twitter.com/dingyuzhen8., Chen Q; Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen 518036, China., Shan H; Institute of Precision Medicine, Peking University Shenzhen Hospital, Shenzhen 518036, China., Liu J; Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen 518036, China., Lv C; Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen 518036, China., Wang Y; Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen 518036, China., Yuan L; Guangdong Provincial Key Laboratory of Brain Science, Disease and Drug Development, HKUST Shenzhen Research Institute, Shenzhen, Guangdong 518057, China., Chen Y; Chinese Academy of Sciences Key Laboratory of Brain Connectome and Manipulation, Shenzhen Key Laboratory of Translational Research for Brain Diseases, The Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, Guangdong 518055, China., Wang Z; Innovative Institute of Basic Medical Sciences of Zhejiang University, Hangzhou 310058, China., Yin Y; Institute of Precision Medicine, Peking University Shenzhen Hospital, Shenzhen 518036, China., Xiao K; Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen 518036, China; HKUST Shenzhen-Hong Kong Collaborative Innovation Research Institute, Futian, Shenzhen, China. Electronic address: xiaokang@ustc.edu., Li J; Division of Cell, Developmental and Integrative Biology, School of Medicine, South China University of Technology, Guangzhou 510006, China. Electronic address: lijch@scut.edu.cn., Liu W; Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen 518036, China; Institute of Geriatric Medicine, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen 518036, China. Electronic address: liuwei@sphmc.org.
المصدر: Journal of molecular biology [J Mol Biol] 2023 Oct 01; Vol. 435 (19), pp. 168243. Date of Electronic Publication: 2023 Aug 22.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: Netherlands NLM ID: 2985088R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1089-8638 (Electronic) Linking ISSN: 00222836 NLM ISO Abbreviation: J Mol Biol Subsets: MEDLINE
أسماء مطبوعة: Publication: Amsterdam : Elsevier
Original Publication: 1959- : London : Academic Press
مواضيع طبية MeSH: Receptor, EphA1*/genetics , Sterile Alpha Motif* , Tumor Suppressor Proteins*, Animals ; Female ; Humans ; Pregnancy ; Embryonic Development ; Receptors, Eph Family/genetics ; Signal Transduction
مستخلص: The Eph (erythropoietin-producing human hepatocellular) receptor family, the largest subclass of receptor tyrosine kinases (RTKs), plays essential roles in embryonic development and neurogenesis. The intracellular Sterile Alpha Motif (SAM) domain presents a critical structural feature that distinguishes Eph receptors from other RTKs and participates in recruiting and binding downstream molecules. This study identified SASH1 (SAM and SH3 domain containing 1) as a novel Eph receptor-binding partner through SAM-SAM domain interactions. Our comprehensive biochemical analyses revealed that SASH1 selectively interacts with Eph receptors via its SAM1 domain, displaying the highest affinity for EphA8. The high-resolution crystal structure of the EphA8-SASH1 complex provided insights into the specific intermolecular interactions between these proteins. Cellular assays confirmed that EphA8 and SASH1 co-localize and co-precipitate in mammalian cells, with cancer mutations (EphA8 R942H or G978D) impairing this interaction. We demonstrated that SAM-SAM interaction is critical for SASH1-mediated regulation of EphA8 kinase activity, shedding new light on the Eph signaling pathway and expanding our understanding of the molecular basis of the tumor suppressor gene SASH1.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)
فهرسة مساهمة: Keywords: Eph signaling; SAM-SAM interaction; SASH1; cancer mutation; kinase activity
المشرفين على المادة: EC 2.7.10.1 (Receptor, EphA1)
EC 2.7.10.1 (Receptors, Eph Family)
0 (SASH1 protein, human)
0 (Tumor Suppressor Proteins)
تواريخ الأحداث: Date Created: 20230824 Date Completed: 20230915 Latest Revision: 20230927
رمز التحديث: 20231215
DOI: 10.1016/j.jmb.2023.168243
PMID: 37619706
قاعدة البيانات: MEDLINE
الوصف
تدمد:1089-8638
DOI:10.1016/j.jmb.2023.168243