Physical association of GPR54 C-terminal with protein phosphatase 2A

• Published in: Biochemical and biophysical research communications Vol. 377; no. 4; pp. 1067 - 1071
• Main Authors: Evans, Barry J., Wang, Zixuan, Mobley, La’Tonya, Khosravi, Davood, Fujii, Nobutaka, Navenot, Jean-Marc, Peiper, Stephen C.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 26.12.2008
• Subjects: 60 APPLIED LIFE SCIENCES; Amino Acid Motifs; Amino Acid Sequence; Animals; ARGININE; Arginine - genetics; Arginine - metabolism; Cell Line; G protein coupled receptor; GENES; GPR54; GTP-ASES; Humans; Kisspeptin; LIGANDS; METASTASES; Metastasis suppressor; Molecular Sequence Data; PHOSPHORYLATION; PP2A; PROLINE; Proline - genetics; Proline - metabolism; Protein complex; Protein phosphatase; Protein Phosphatase 2 - chemistry; Protein Phosphatase 2 - genetics; Protein Phosphatase 2 - metabolism; Protein Subunits - genetics; Protein Subunits - metabolism; RECEPTORS; Receptors, G-Protein-Coupled - chemistry; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - metabolism; Receptors, Kisspeptin-1; src Homology Domains - genetics; Two-Hybrid System Techniques; YEASTS; Kisspeptin; Protein complex; G protein coupled receptor; Metastasis suppressor; GPR54; Protein phosphatase; PP2A
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2008.10.108

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.