MAP Kinase Pathway–dependent Phosphorylation of the L1-CAM Ankyrin Binding Site Regulates Neuronal Growth

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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.