title: Physical association of GPR54 C-terminal with protein phosphatase 2A.
abstract: KiSS1 was discovered as a metastasis suppressor gene and subsequently found to encode kisspeptins (KP), ligands for a G protein coupled receptor (GPCR), GPR54. This ligand-receptor pair was later shown to play a critical role in the neuro-endocrine regulation of puberty. The C-terminal cytoplasmic (C-ter) domain of GPR54 contains a segment rich in proline and arginine residues that corresponds to the primary structure of four overlapping SH3 binding motifs. Yeast two hybrid experiments identified the catalytic subunit of protein phosphatase 2A (PP2A-C) as an interacting protein. Pull-down experiments with GST fusion proteins containing the GPR54 C-ter confirmed binding to PP2A-C in cell lysates and these complexes contained phosphatase activity. The proline arginine rich segment is necessary for these interactions. The GPR54 C-ter bound directly to purified recombinant PP2A-C, indicating the GPR54 C-ter may form complexes involving the catalytic subunit of PP2A that regulate phosphorylation of critical signaling intermediates.
authors.affiliation: Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Evans
authors.forename: Zixuan
authors.initials: Z
authors.lastname: Wang
authors.forename: La'Tonya
authors.initials: L
authors.lastname: Mobley
authors.forename: Davood
authors.initials: D
authors.lastname: Khosravi
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Fujii
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Navenot
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Peiper
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011392:Proline / Q000235:genetics / Q000378:metabolism; D054648:Protein Phosphatase 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000074502:Receptors, Kisspeptin-1; D020798:Two-Hybrid System Techniques; D018909:src Homology Domains / Q000235:genetics
chemical_list: C118688:KISS1R protein, human; D021122:Protein Subunits; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1; D001120:Arginine; D011392:Proline; D054648:Protein Phosphatase 2