title: Low expression level of OB-Rb results from constitutive translocational attenuation attributable to a less efficient signal sequence.
abstract: OB-Rb is a crucial factor for leptin signaling. This study was initially motivated by the observation that OB-Rb expression is constitutively inhibited in the early secretory pathway. Our analyses reveal that OB-Rb contains a less hydrophobic, but functionally active N-terminal signal sequence. Constitutive translocational attenuation attributable to a less efficient signal sequence proved to be a reason for low protein level of OB-Rb. By contrast, enhanced signal sequence efficiency rescues translocation and cell surface expression of OB-Rb, and eventually potentiates leptin signaling. These observations provide considerable insight into the therapeutic enhancement of OB-Rb translocation as a potential strategy for leptin resistance.
authors.affiliation: Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Ilho
authors.initials: I
authors.lastname: Choi
authors.affiliation: Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Joong-Yeol
authors.initials: JY
authors.lastname: Park
authors.affiliation: Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, Republic of Korea; Department of Anatomy and Cell Biology, University of Ulsan College of Medicine, Seoul, Republic of Korea; Cell Dysfunction Research Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Youngsup
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Anatomy and Cell Biology, University of Ulsan College of Medicine, Seoul, Republic of Korea; Cell Dysfunction Research Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Seung-Yong
authors.initials: SY
authors.lastname: Yoon
authors.affiliation: Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, Republic of Korea; Department of Anatomy and Cell Biology, University of Ulsan College of Medicine, Seoul, Republic of Korea; Cell Dysfunction Research Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Eun-Ju
authors.initials: EJ
authors.lastname: Chang
authors.affiliation: Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, Republic of Korea; Department of Anatomy and Cell Biology, University of Ulsan College of Medicine, Seoul, Republic of Korea; Cell Dysfunction Research Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. Electronic address: swkang@amc.seoul.kr.
authors.forename: Sang-Wook
authors.initials: SW
authors.lastname: Kang
mesh_terms: D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000378:metabolism; D015870:Gene Expression; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D020738:Leptin / Q000502:physiology; D008969:Molecular Sequence Data; D021382:Protein Sorting Signals; D021381:Protein Transport; D054411:Receptors, Leptin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C515448:LEPR protein, human; D020738:Leptin; D021382:Protein Sorting Signals; D054411:Receptors, Leptin
keywords: Leptin receptor; Leptin resistance; Secretory pathway; Signal sequence; Translocation