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Protein Phosphatase 1α is involved in the regulation of the thyrotropin‐releasing hormone receptor
Author(s) -
Gehret Austin U.,
Hinkle Patricia M.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.lb180
Subject(s) - dephosphorylation , phosphatase , protein phosphatase 1 , phosphorylation , g protein coupled receptor , receptor , signal transduction , microbiology and biotechnology , biology , biochemistry , chemistry
G protein‐coupled receptors (GPCRs) are widely expressed transmembrane proteins involved in signal transduction of neurotransmitters, hormones and various other ligands. Their signaling is desensitized through phosphorylation and dissociation from their cognate G proteins. They are resensitized by mechanisms involving dephosphorylation, but details about the phosphatases responsible are generally lacking. We describe here the use of an siRNA‐based knock down screening approach to identify phosphatase(s) acting on a GPCR, the thyrotropin‐releasing hormone (TRH) receptor, in conjuction with phosphatase inhibitor studies. Protein phosphatase PP1α was specifically identified as critical in TRH receptor regulation. Inhibition of PP1α synthesis with an siRNA directed against the PP1α catalytic subunit and overexpression of a dominant negative mutant preserved receptor phosphorylation under conditions favoring dephosphorylation whereas overexpression of PP1α accelerated dephosphorylation. Parallel studies with PP1β and PP1γ showed no significant change on dephosphorylation. We conclude that the PP1 class of phosphatases is directly responsible for dephosphorylating the TRH receptor and likely to be involved in regulation of other GPCRs.