pp60(c-src) is a negative regulator of laminin-1-mediated neurite outgrowth in chick sensory neurons

Mol Cell Neurosci. 2002 Sep;21(1):81-93. doi: 10.1006/mcne.2002.1157.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology*
  • Cells, Cultured
  • Chick Embryo
  • Down-Regulation / drug effects
  • Down-Regulation / physiology
  • Enzyme Inhibitors / pharmacology
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / embryology*
  • Ganglia, Spinal / enzymology
  • Genistein / pharmacology
  • Growth Cones / drug effects
  • Growth Cones / enzymology
  • Growth Cones / ultrastructure
  • Laminin / metabolism*
  • Lasers
  • Neurites / drug effects
  • Neurites / enzymology*
  • Neurites / ultrastructure
  • Neurons, Afferent / cytology
  • Neurons, Afferent / drug effects
  • Neurons, Afferent / enzymology*
  • Phosphotyrosine / metabolism
  • Proto-Oncogene Proteins pp60(c-src) / antagonists & inhibitors
  • Proto-Oncogene Proteins pp60(c-src) / immunology
  • Proto-Oncogene Proteins pp60(c-src) / metabolism*
  • Pseudopodia / drug effects
  • Pseudopodia / enzymology


  • Enzyme Inhibitors
  • Laminin
  • laminin 1
  • Phosphotyrosine
  • Genistein
  • Proto-Oncogene Proteins pp60(c-src)