CD82 palmitoylation site mutations at Cys5+Cys74 affect EGFR internalization and metabolism through recycling pathway  

作　　者：Jingya Bu Weiliang Zhong Meixian Li Shuiqing He Mingzhe Zhang Yu Zhang Ying Li 

机构地区：[1]Department of Clinical Laboratory,the Second Affiliated Hospital of Dalian Medical University,Dalian 116023,China [2]Department of Orthopaedics Surgery,the First Affiliated Hospital of Dalian Medical University,Dalian 116011,China [3]Key Laboratory of Molecular Mechanism for Repair and Remodeling of Orthopaedic Diseases,Liaoning Province,Dalian 116011,China [4]Department of Clinical Laboratory,Jiangxi Maternal and Child Health Hospital,Nanchang 330000,China

出　　处：《Acta Biochimica et Biophysica Sinica》2022年第3期400-408,共9页生物化学与生物物理学报（英文版）

基　　金：This work was supported by the grants from the Key Disciplines of the Second Affiliated Hospital of Dalian Medical University(No.dy2yxkgg202004);the Scientific Research Fund of Education Department of Liaoning Province(No.LZ2019008);the Medical Sciences research program of Dalian of China(No.1812032);the National Natural Science Foundation of China(No.81601619).

摘　　要：Tetraspanin CD82 often participates in regulating the function of epidermal growth factor receptor(EGFR)and hepatocyte growth factor receptor(c-Met).Palmitoylation is a post-translational modification that contributes to tetraspanin web formation and affects tetraspanin-dependent cell signaling.However,the molecular mechanisms by which CD82 palmitoylation affects the localization and stability of EGFR and c-Met have not yet been elucidated.This study focuses on the expression and distribution of EGFR and c-Met in breast cancer as well as the related metabolic pathways and molecular mechanisms associated with different CD82 palmitoylation site mutations.The results show that CD82 with a palmitoylation mutation at Cys5+Cys74 can promote the internalization of EGFR.EGFR is internalized and strengthened by direct binding to CD82 with the tubulin assistance and located at the recycling endosome.After studying the recycling pathway marker proteins Rab11a and FIP2,we found that formation of the EGFR/CD82/Rab11a/FlP2 complex promotes the internalization and metabolism of EGFR through the recycling pathway and results in the re-expression of EGFR and CD82 on the cell membrane.

关 键 词：TETRASPANIN CD82 PALMITOYLATION EGFR Rab11a 

分 类 号：R730[医药卫生—肿瘤]