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Acetylation modulates prolactin receptor dimerization.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America . 11/9/2010, Vol. 107 Issue 45, p19314-19319. 6p. 4 Diagrams, 1 Graph. - Publication Year :
- 2010
-
Abstract
- Cytokine-activated receptors undergo extracellular domain dimerization, which is necessary to activate intracellular signaling path- ways. 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *CYTOKINES
*LYSINE
*CELL receptors
*CARRIER proteins
*DIMERS
Subjects
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 107
- Issue :
- 45
- Database :
- Academic Search Index
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 57843370
- Full Text :
- https://doi.org/10.1073/pnas.1010253107