Low expression level of OB-Rb results from constitutive translocational attenuation attributable to a less efficient signal sequence

•Leptin receptor (LepR) contains less efficient signal sequence.•Enhanced signal sequence efficiency promotes LepR expression.•Enhanced signal sequence efficiency potentiates leptin signaling.•Therapeutic enhancement of LepR translocation for leptin resistance. OB-Rb is a crucial factor for leptin s...

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Bibliographic Details
Published in:FEBS letters 2014-06, Vol.588 (14), p.2321-2327
Main Authors: Choi, Ilho, Park, Joong-Yeol, Song, Youngsup, Yoon, Seung-Yong, Chang, Eun-Ju, Kang, Sang-Wook
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Cell Membrane - metabolism
Dox
doxycycline
Gene Expression
Gene Expression Regulation
HEK293 Cells
HeLa Cells
Humans
Hydrophobic and Hydrophilic Interactions
JAK
Janus kinase
Leptin - physiology
Leptin receptor
Leptin resistance
Molecular Sequence Data
prion protein
Prl
prolactin
Protein Sorting Signals
Protein Transport
proteinase K
PrP
Receptors, Leptin - chemistry
Receptors, Leptin - genetics
Receptors, Leptin - metabolism
rough microsome
Secretory pathway
signal recognition particle
Signal sequence
signal transducer and activator of transcription
Signal Transduction
SRP
STAT
TMD
Translocation
transmembrane domain
vascular endotherial cell adhesion molecule-1
VCAM-1
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Summary:•Leptin receptor (LepR) contains less efficient signal sequence.•Enhanced signal sequence efficiency promotes LepR expression.•Enhanced signal sequence efficiency potentiates leptin signaling.•Therapeutic enhancement of LepR translocation for leptin resistance. 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.
ISSN:0014-5793
1873-3468
DOI:10.1016/j.febslet.2014.05.025