An inward rectifier K+ current modulates in neuroblastoma cells the tyrosine phosphorylation of the pp125FAK and associated proteins: role in neuritogenesis

Biochem Biophys Res Commun. 1995 May 25;210(3):823-9. doi: 10.1006/bbrc.1995.1732.

Abstract

The relationships between the integrin-mediated activation of inward rectifyier K+ channels (KIR), the phosphorylation of pp125FAK and the rescue of neuritogenesis were studied in 41A3 mouse neuroblastoma cells. Neuritogenesis, elicited by adhesion to FN-enriched substrata, was reversibly impaired by pretreating these cells with the tyrosine kinase inhibitor Herbimycin A. This impairment mimicked that operated by Cs+ ions, which selectively inhibited the integrin-mediated activation of KIR channels. Various phosphotyrosine containing cellular proteins underwent a marked increase upon cell adhesion to FN-coated dishes. This increase was significantly reduced by Cs+ addition. Immunoprecipitation of pp125FAK revealed that the phosphorylation of this kinase and several associated proteins was significantly and reversibly inhibited by Cs+, indicating that integrin-mediated activation of KIR channels is a limiting step upstream to the phosphorylation of pp125FAK in the commitment to neuritogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzoquinones
  • Cell Adhesion Molecules / metabolism*
  • Cell Line
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • Lactams, Macrocyclic
  • Membrane Potentials
  • Mice
  • Neoplasm Proteins / isolation & purification
  • Neoplasm Proteins / metabolism
  • Neurites / drug effects
  • Neurites / physiology*
  • Neuroblastoma
  • Patch-Clamp Techniques
  • Phosphoproteins / isolation & purification
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Phosphotyrosine
  • Potassium Channels / physiology*
  • Potassium Channels, Inwardly Rectifying*
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Protein-Tyrosine Kinases / metabolism*
  • Quinones / pharmacology
  • Receptor, Insulin / metabolism*
  • Rifabutin / analogs & derivatives
  • Tumor Cells, Cultured
  • Tyrosine / analogs & derivatives
  • Tyrosine / analysis
  • Tyrosine / metabolism

Substances

  • Benzoquinones
  • Cell Adhesion Molecules
  • Lactams, Macrocyclic
  • Neoplasm Proteins
  • Phosphoproteins
  • Potassium Channels
  • Potassium Channels, Inwardly Rectifying
  • Quinones
  • Rifabutin
  • Phosphotyrosine
  • Tyrosine
  • herbimycin
  • Protein-Tyrosine Kinases
  • Receptor, Insulin
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • Ptk2 protein, mouse