Low expression level of OB-Rb results from constitutive translocational attenuation attributable to a less efficient signal sequence |
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| Authors: | Ilho Choi Joong-Yeol Park Youngsup Song Seung-Yong Yoon Eun-Ju Chang Sang-Wook Kang |
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| Affiliation: | 1. Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, Republic of Korea;2. Department of Anatomy and Cell Biology, University of Ulsan College of Medicine, Seoul, Republic of Korea;3. Cell Dysfunction Research Center, University of Ulsan College of Medicine, Seoul, Republic of Korea;4. Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea |
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| 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. |
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| Keywords: | VCAM-1, vascular endotherial cell adhesion molecule-1 PrP, prion protein Prl, prolactin JAK, Janus kinase STAT, signal transducer and activator of transcription SRP, signal recognition particle Dox, doxycycline TMD, transmembrane domain PK, proteinase K RM, rough microsome |
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