scholarly journals Overlapping Binding Sites in Protein Phosphatase 2A for Association with Regulatory A and α-4 (mTap42) Subunits

2004 ◽  
Vol 279 (37) ◽  
pp. 38912-38920 ◽  
Author(s):  
Todd D. Prickett ◽  
David L. Brautigan
Keyword(s):  
Protein Phosphatase ◽  
Binding Sites ◽  
Protein Phosphatase 2A ◽  
Phosphatase 2A

scholarly journals Protein phosphatase 2A mediates resensitization of the neurokinin 1 receptor

2011 ◽  
Vol 301 (4) ◽  
pp. C780-C791 ◽  
Author(s):  
Jane E. Murphy ◽  
Dirk Roosterman ◽  
Graeme S. Cottrell ◽  
Benjamin E. Padilla ◽  
Micha Feld ◽  
...  
Keyword(s):  
Cell Surface ◽  
Protein Phosphatase ◽  
Binding Sites ◽  
Protein Phosphatase 2A ◽  
Surface Binding ◽  
Neurokinin 1 Receptor ◽  
Phosphatase 2A ◽  
Neurokinin 1 ◽  
Rna Knockdown ◽  
Interfering Rna

Activated G protein-coupled receptors (GPCRs) are phosphorylated and interact with β-arrestins, which mediate desensitization and endocytosis. Endothelin-converting enzyme-1 (ECE-1) degrades neuropeptides in endosomes and can promote recycling. Although endocytosis, dephosphorylation, and recycling are accepted mechanisms of receptor resensitization, a large proportion of desensitized receptors can remain at the cell surface. We investigated whether reactivation of noninternalized, desensitized (phosphorylated) receptors mediates resensitization of the substance P (SP) neurokinin 1 receptor (NK1R). Herein, we report a novel mechanism of resensitization by which protein phosphatase 2A (PP2A) is recruited to dephosphorylate noninternalized NK1R. A desensitizing concentration of SP reduced cell-surface SP binding sites by only 25%, and SP-induced Ca2+ signals were fully resensitized before cell-surface binding sites started to recover, suggesting resensitization of cell-surface-retained NK1R. SP induced association of β-arrestin1 and PP2A with noninternalized NK1R. β-Arrestin1 small interfering RNA knockdown prevented SP-induced association of cell-surface NK1R with PP2A, indicating that β-arrestin1 mediates this interaction. ECE-1 inhibition, by trapping β-arrestin1 in endosomes, also impeded SP-induced association of cell-surface NK1R with PP2A. Resensitization of NK1R signaling required both PP2A and ECE-1 activity. Thus, after stimulation with SP, PP2A interacts with noninternalized NK1R and mediates resensitization. PP2A interaction with NK1R requires β-arrestin1. ECE-1 promotes this process by releasing β-arrestin1 from NK1R in endosomes. These findings represent a novel mechanism of PP2A- and ECE-1-dependent resensitization of GPCRs.

scholarly journals Protein Phosphatase 2A Positively Regulates Ras Signaling by Dephosphorylating KSR1 and Raf-1 on Critical 14-3-3 Binding Sites

2003 ◽  
Vol 13 (16) ◽  
pp. 1356-1364 ◽  
Author(s):  
Stéphane Ory ◽  
Ming Zhou ◽  
Thomas P Conrads ◽  
Timothy D Veenstra ◽  
Deborah K Morrison
Keyword(s):  
Protein Phosphatase ◽  
Binding Sites ◽  
Protein Phosphatase 2A ◽  
Ras Signaling ◽  
Phosphatase 2A
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