tailieunhanh - Báo cáo khoa học: Lysophosphatidic acid inhibits ghrelin secretion in the human gastric adenocarcinoma AGS cell line ) role of mitogenic activated protein kinase signaling pathway

Ghrelin, the endogenous ligand for the growth hormone secretagogue receptor type 1a (GHS-R1a), is a 28 amino acid residue with a post-trans-lational octanoyl modification on Ser3. Despite the biomedical interest in this hormone, the fine details of its regulation and the mechanisms control-ling its secretion are largely unknown. | ễFEBS Journal Lysophosphatidic acid inhibits ghrelin secretion in the human gastric adenocarcinoma AGS cell line - role of mitogenic activated protein kinase signaling pathway Yolanda Pazos1 2 Carlos J. P. Alvarez3 Jesus P. Camina1 2 and Felipe F. Casanueva1 2 3 1 Molecular Endocrinology Research Area Complejo Hospitalario Universitario de Santiago CHUS Santiago de Compostela Spain 2 CIBER Fisiopatologia Obesidad y Nutricion CB06 03 Instituto de Salud Carlos III Spain 3 Department of Medicine Santiago de Compostela University Spain Keywords c-Src epidermal growth factor receptor ERK1 2 ghrelin lysophosphatidic acid Correspondence Y. Pazos Molecular Endocrinology Research Area Complejo Hospitalario Universitario de Santiago CHUS PO Box 563 E-15780 Santiago de Compostela Spain Fax Tel 34 981 572121 E-mail qorandul@ Received 24 May 2007 revised 7 August 2007 accepted 4 September 2007 doi Ghrelin the endogenous ligand for the growth hormone secretagogue receptor type 1a GHS-R1a is a 28 amino acid residue with a post-translational octanoyl modification on Ser3. Despite the biomedical interest in this hormone the fine details of its regulation and the mechanisms controlling its secretion are largely unknown. The present study analyzes the molecular steps involved in the full lysophosphatidic acid LPA receptor-mediated activation of the mitogenic extracellular signal-regulated kinase ERK pathway and its consequent role as an inhibitor of ghrelin secretion in the gastric adenocarcinoma cell line AGS. ERK1 2 phosphorylation mediated by LPA proceeds via activation of the type 2 LPA receptor activation of the nonreceptor tyrosine kinase c-Src and subsequent transactivation of the epidermal growth factor receptor. Furthermore LPA-induced ERK activation was found to be independent of matrix metalloproteinases thus c-Src acted as the scaffold-transactivating epidermal growth factor receptor. Finally a correlation was observed between the .