title: Focal adhesion kinase dependent activation of the PI3 kinase pathway by the functional soluble form of neurotensin receptor-3 in HT29 cells.
abstract: The neurotensin (NT) receptor-3 (NTSR3), also called sortilin, is thought to display several functions including a role as a receptor or a co-receptor, in the sorting to plasma membrane and to lysosomes, and in the regulated secretion. The aim of this study was to investigate the function of the soluble form of NTSR3 (sNTSR3) released from several cell lines including colonic cancer cells. The human adenocarcinoma epithelial cell line HT29 has been used to monitor the release, the binding and internalization of sNTSR3 by radioreceptor assays and confocal microscopy. The modulation of the intracellular signaling pathways by the protein has been investigated by using Fura-2 fluorescence calcium imaging microscopy and Western blots analysis. We demonstrated that sNTSR3 specifically binds and internalizes into HT29 cells. This binding, independent from the transactivation of the epidermal growth factor receptor, leads to the increase of intracellular calcium concentration and to the activation of a FAK/Src-dependent activation of the PI3 kinase pathway. In conclusion, sNTSR3 released from the membrane bound NTSR3 is a functional protein able to activate intracellular pathways involved in cell survival but probably not in cell growth.
authors: CNRS, Institut de Pharmacologie Moléculaire et Cellulaire, UMR 7275, Université de Nice Sophia Antipolis, 660 route des Lucioles, 06560 Valbonne, France.
authors: Fabienne
authors: F
authors: Massa
authors: Christelle
authors: C
authors: Devader
authors: Sophie
authors: S
authors: Béraud-Dufour
authors: Frédéric
authors: F
authors: Brau
authors: Thierry
authors: T
authors: Coppola
authors: Jean
authors: J
authors: Mazella
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D048708:Cell Growth Processes / Q000502:physiology; D003110:Colonic Neoplasms / Q000201:enzymology / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D019073:HT29 Cells; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D051571:Protein Kinase C-alpha / Q000378:metabolism; D015398:Signal Transduction; D000099183:Sortilin
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D002118:Calcium; D066246:ErbB Receptors; D051417:Focal Adhesion Kinase 1; D019869:Phosphatidylinositol 3-Kinases; D051571:Protein Kinase C-alpha; D000099183:Sortilin; C496050:PTK2 protein, human