Lysophosphatidic Acid Receptor 3 (LPA3): Signaling and Phosphorylation Sites
Por:
Solís, KH, Romero-Avila, MT, Rincón-Heredia, R, García-Sáinz, JA
Publicada:
1 jun 2024
Resumen:
LPA(3) receptors were expressed in TREx HEK 293 cells, and their signaling and phosphorylation were studied. The agonist, lysophosphatidic acid (LPA), increased intracellular calcium and ERK phosphorylation through pertussis toxin-insensitive processes. Phorbol myristate acetate, but not LPA, desensitizes LPA(3)-mediated calcium signaling, the agonists, and the phorbol ester-induced LPA(3) internalization. Pitstop 2 (clathrin heavy chain inhibitor) markedly reduced LPA-induced receptor internalization; in contrast, phorbol ester-induced internalization was only delayed. LPA induced rapid beta-arrestin-LPA(3) receptor association. The agonist and the phorbol ester-induced marked LPA(3) receptor phosphorylation, and phosphorylation sites were detected using mass spectrometry. Phosphorylated residues were detected in the intracellular loop 3 (S221, T224, S225, and S229) and in the carboxyl terminus (S321, S325, S331, T333, S335, Y337, and S343). Interestingly, phosphorylation sites are within sequences predicted to constitute beta-arrestin binding sites. These data provide insight into LPA(3) receptor signaling and regulation.
Filiaciones:
Solís, KH:
Univ Nacl Autonoma Mexico, Dept Biol Celular & Desarrollo, Inst Fisiol Celular, Ciudad Univ,Ap Postal 70-600, Mexico City 04510, Mexico
Romero-Avila, MT:
Univ Nacl Autonoma Mexico, Dept Biol Celular & Desarrollo, Inst Fisiol Celular, Ciudad Univ,Ap Postal 70-600, Mexico City 04510, Mexico
Rincón-Heredia, R:
Univ Nacl Autonoma Mexico, Unidad Imagenol, Inst Fisiol Celular, Ap Postal 70-600, Mexico City 04510, Mexico
García-Sáinz, JA:
Univ Nacl Autonoma Mexico, Dept Biol Celular & Desarrollo, Inst Fisiol Celular, Ciudad Univ,Ap Postal 70-600, Mexico City 04510, Mexico
gold, All Open Access; Gold Open Access
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