title: pp60(c-src) is a negative regulator of laminin-1-mediated neurite outgrowth in chick sensory neurons.
abstract: Multiple protein tyrosine kinases regulate neurite outgrowth in the developing nervous system. To begin to unravel the complexity of this regulation, we addressed the role of one specific kinase, pp60(c-src), in chick dorsal root ganglion (DRG) neurons grown on laminin-1, a well-characterized system to study neurite outgrowth. Pharmacological inhibition of all tyrosine kinases by genestein treatment of chick DRG neurons significantly increased neurite number and length by approximately 50%. Similar increases in these parameters occurred when src-family kinases were inhibited using PP2. To implicate pp60(c-src) directly in neurite outgrowth, we inactivated it in DRG neuronal growth cones using Chromophore-Assisted Laser Inactivation (CALI). CALI of pp60(c-src) resulted in an 85% inactivation of its kinase activity and a 63% reduction in phosphotyrosine immunofluorescence in neurons. Microscale CALI of pp60(c-src) in DRG growth cones caused a significant and acute two-fold increase in neurite extension rate during irradiation. These findings demonstrate that pp60(c-src) is a negative regulator of laminin-1-mediated neurite outgrowth in chick sensory neurons.
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002642:Chick Embryo; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology / Q000196:embryology* / Q000201:enzymology; D019833:Genistein / Q000494:pharmacology; D020439:Growth Cones / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D007797:Laminin / Q000378:metabolism*; D007834:Lasers; D016501:Neurites / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D019000:Phosphotyrosine / Q000378:metabolism; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D011554:Pseudopodia / Q000187:drug effects / Q000201:enzymology
chemical_list: D004791:Enzyme Inhibitors; D007797:Laminin; C121346:laminin 1; D019000:Phosphotyrosine; D019833:Genistein; D016392:Proto-Oncogene Proteins pp60(c-src)