title: Agonists and protein kinase C-activation induce phosphorylation and internalization of FFA1 receptors.
abstract: FFA1 (previously known as GPR40) is a free fatty acid receptor involved in the regulation of inflammatory processes and insulin secretion. The cellular actions resulting from FFA1 activation have received considerable attention. However, little is known on the regulation of the receptor function. In the present work, using cells transfected with this receptor, docosahexaenoic acid and α-linolenic acid increased intracellular calcium concentration and ERK 1/2 phosphorylation. It was also observed that FFA1 is a phosphoprotein whose phosphorylation state was increased (2- to 3-fold) by agonists (i.e., free fatty acids) and also by phorbol myristate acetate. Agonist- and phorbol ester-mediated FFA1 phosphorylation was markedly reduced by inhibitors of protein kinase C. Receptor stimulation by free fatty acids and protein kinase C activation also induced receptor internalization as evidenced by confocal microscopy. In summary, our data show that FFA1 is a phosphoprotein whose phosphorylation state is modulated by agonists and protein kinase C activation; such covalent modification is associated with receptor internalization.
authors.affiliation: Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ap. Postal 70-248, México D.F. 04510, Mexico.
authors.forename: Carla
authors.initials: C
authors.lastname: Sosa-Alvarado
authors.affiliation: Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ap. Postal 70-248, México D.F. 04510, Mexico.
authors.forename: Aurelio
authors.initials: A
authors.lastname: Hernández-Méndez
authors.affiliation: Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ap. Postal 70-248, México D.F. 04510, Mexico.
authors.forename: M Teresa
authors.initials: MT
authors.lastname: Romero-Ávila
authors.affiliation: Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ap. Postal 70-248, México D.F. 04510, Mexico.
authors.forename: Omar B
authors.initials: OB
authors.lastname: Sánchez-Reyes
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyoto University Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Takei
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyoto University Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Gozoh
authors.initials: G
authors.lastname: Tsujimoto
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyoto University Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Hirasawa
authors.affiliation: Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ap. Postal 70-248, México D.F. 04510, Mexico. Electronic address: agarcia@ifc.unam.mx.
authors.forename: J Adolfo
authors.initials: JA
authors.lastname: García-Sáinz
mesh_terms: D002118:Calcium / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D017962:alpha-Linolenic Acid / Q000494:pharmacology
chemical_list: C473034:FFAR1 protein, human; D043562:Receptors, G-Protein-Coupled; D017962:alpha-Linolenic Acid; D004281:Docosahexaenoic Acids; D011493:Protein Kinase C; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D002118:Calcium
keywords: Docosahexaenoic acid (PubChem CID: 445580); ERK phosphorylation; FFA1 internalization; FFA1 phosphorylation; GPR40; Lysophosphatidic acid (PubChem CID: 5497152); Phorbol 12-myristate, 13-acetate (PubChem CID: 27924); Protein kinase C; α-Linolenic acid (PubChem CID: 5280934)