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Acetylation modulates prolactin receptor dimerization

Authors
 Li Ma  ;  Jin-song Gao  ;  Yingjie Guan  ;  Xiaoyan Shi  ;  Hao Zhang  ;  Marina K. Ayrapetov  ;  Zhe Zhang  ;  Li Xu  ;  Young-Min Hyun  ;  Minsoo Kim  ;  Shougang Zhuang  ;  Y. Eugene Chin 
Citation
 Proceedings of the National Academy of Sciences of the United States of America, Vol.107(45) : 19314-19319, 2010 
Journal Title
 Proceedings of the National Academy of Sciences of the United States of America 
ISSN
 0027-8424 
Issue Date
2010
MeSH
Acetylation ; Binding Sites ; CREB-Binding Protein/metabolism ; Cell Line ; Humans ; Lysine/metabolism ; Protein Multimerization* ; Receptors, Prolactin/metabolism* ; STAT5 Transcription Factor/metabolism
Keywords
acetylation ; CREB-binding protein ; dimerization ; prolactin receptor ; STAT5
Abstract
Cytokine-activated receptors undergo extracellular domain dimerization, which is necessary to activate intracellular signaling pathways. Here, we report that in prolactin (PRL)-treated cells, PRL receptor (PRLR) undergoes cytoplasmic loop dimerization that is acetylation-dependent. PRLR-recruited CREB-binding protein (CBP) acetylates multiple lysine sites randomly distributed along the cytoplasmic loop of PRLR. Two PRLR monomers appear to interact with each other at multiple parts from the membrane-proximal region to the membrane-distal region, relying on the coordination among multiple lysine sites neutralized via acetylation. Cytoplasmic loop-dimerized PRLR activates STAT5, which is also acetylated by CBP and undergoes acetylation-dependent dimerization. PRLR dimerization and subsequent signaling are enhanced by treating the cells with deacetylase sirtuin (SIRT) inhibitor nicotinamide or histone deacetylase (HDAC) inhibitor trichostatin A but inhibited by expressing exogenous deacetylase SIRT2 or HDAC6. Our results suggest that acetylation and deacetylation provide the rheostat-like regulation for the cytokine receptor PRLR in its cytoplasmic loop dimerization and subsequent STAT5 activation.
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DOI
10.1073/pnas.1010253107
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
Yonsei Authors
Hyun, Young-Min(현영민) ORCID logo https://orcid.org/0000-0002-0567-2039
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/158123
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