Distinct neurite outgrowth signaling pathways converge on ERK activation.
Several distinct classes of proteins positively regulate axonal growth; some of these are known to activate the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling cascade, at least in nonneuronal cells. We have found that N-cadherin, as well as laminin (LN) and basic fibroblast growth factor (bFGF), can activate ERK in embryonic chick retinal neurons. Additionally, adhesion of retinal neurons to LN or N-cadherin substrates induced a redistribution of ERK from the cytoplasm toward the plasma membrane. Neurite outgrowth induced by bFGF, LN, or N-cadherin was strongly inhibited by treatment with inhibitors of ERK kinase activation, but not by an inhibitor of p38 MAPK. We conclude (1) that N-cadherin and LN can activate ERK in retinal neurons and (2) that activation of ERK is required for full neurite outgrowth induced by these proteins. Our results suggest that ERK activation is one point of convergence for signaling pathways generated by a variety of axon growth inducers.
Perron
J C
JC
Department of Molecular & Cell. Pharmacology, R-189, Neuroscience Program, University of Miami School of Medicine, 1600 NW 10 Avenue, Miami, Florida, 33136, USA.
Bixby
J L
JL
D016475:3T3 Cells / Q000166:cytology / Q000201:enzymology; D000818:Animals; D000906:Antibodies; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D015820:Cadherins / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000032:analysis / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D002462:Cell Membrane / Q000201:enzymology; D002478:Cells, Cultured; D002642:Chick Embryo; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D007527:Isoenzymes / Q000378:metabolism*; D007797:Laminin / Q000494:pharmacology; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D004676:Myelin Basic Protein / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects / Q000201:enzymology*; D009474:Neurons / Q000166:cytology / Q000201:enzymology / Q000648:ultrastructure; D012160:Retina / Q000166:cytology; D015398:Signal Transduction / Q000502:physiology*; D013379:Substrate Specificity; D048051:p38 Mitogen-Activated Protein Kinases
D000906:Antibodies; D019208:Brain-Derived Neurotrophic Factor; D015820:Cadherins; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007527:Isoenzymes; D007797:Laminin; D004676:Myelin Basic Protein; D016222:Fibroblast Growth Factor 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one