title: MAP kinase pathway-dependent phosphorylation of the L1-CAM ankyrin binding site regulates neuronal growth.
abstract: The growth of neuronal processes depends critically on the function of adhesion proteins that link extracellular ligands to the cytoskeleton. The neuronal adhesion protein L1-CAM serves as a receptor for nerve growth-promoting proteins, a process that is inhibited by the interaction between L1-CAM and the cytoskeleton adaptor ankyrin. Using a novel reporter based on intramolecular bioluminescence resonance energy transfer, we have determined that the MAP kinase pathway regulates the phosphorylation of the FIGQY motif in the adhesion protein L1-CAM and its interaction with ankyrin B. MAP kinase pathway inhibitors block L1-CAM-mediated neuronal growth. However, this blockade is partially rescued by inhibitors of L1-CAM-ankyrin binding. These results demonstrate that the MAP kinase pathway regulates L1-CAM-mediated nerve growth by modulating ankyrin binding, suggesting that nerve growth can be regulated at the level of individual receptors.
authors.affiliation: Department of Pharmacology and Biological Chemistry, Mt. Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Whittard
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sakurai
authors.forename: Melanie R
authors.initials: MR
authors.lastname: Cassella
authors.forename: Mihaela
authors.initials: M
authors.lastname: Gazdoiu
authors.forename: Dan P
authors.initials: DP
authors.lastname: Felsenfeld
mesh_terms: D017487:Ankyrins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001665:Binding Sites; D045744:Cell Line, Tumor; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism*; D016501:Neurites / Q000502:physiology*; D009447:Neuroblastoma; D010766:Phosphorylation
chemical_list: D017487:Ankyrins; D039842:Neural Cell Adhesion Molecule L1