Pyk2 and FAK regulate neurite outgrowth induced by growth factors and integrins

Nat Cell Biol. 2000 Sep;2(9):574-81. doi: 10.1038/35023515.

Abstract

Integration of signalling pathways initiated by receptor tyrosine kinases and integrins is essential for growth-factor-mediated biological responses. Here we show that co-stimulation of growth-factor receptors and integrins activates the focal-adhesion kinase (FAK) family to promote outgrowth of neurites in PC12 and SH-SY5Y cells. Pyk2 and FAK associate with adhesion-based complexes that contain epidermal growth factor (EGF) receptors, through their carboxy- and amino-terminal domains. Expression of the C-terminal domain of Pyk2 or of FAK is sufficient to block neurite outgrowth, but not activation of extracellular-signal-regulated kinase (ERK). Moreover, activation and autophosphorylation of Pyk2/FAK, as well as of effectors of their adhesion-targeting domains, such as paxillin, are important for propagation of signals that control neurite formation. Thus, Pyk2/FAK have important functions in signal integration proximal to integrin/growth-factor receptor complexes in neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytoskeletal Proteins / metabolism
  • Enzyme Activation
  • Epidermal Growth Factor / metabolism
  • Epidermal Growth Factor / pharmacology
  • ErbB Receptors / metabolism
  • Focal Adhesion Kinase 1
  • Focal Adhesion Kinase 2
  • Focal Adhesion Protein-Tyrosine Kinases
  • Growth Substances / metabolism*
  • Growth Substances / pharmacology
  • Humans
  • Insulin / metabolism
  • Insulin / pharmacology
  • Insulin-Like Growth Factor I / metabolism
  • Insulin-Like Growth Factor I / pharmacology
  • Integrins / metabolism*
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases / metabolism
  • Nerve Growth Factor / metabolism
  • Nerve Growth Factor / pharmacology
  • Neurites / physiology*
  • PC12 Cells
  • Paxillin
  • Phosphoproteins / metabolism
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Protein-Tyrosine Kinases / metabolism*
  • Rats
  • Signal Transduction / physiology*
  • Tumor Cells, Cultured

Substances

  • Cytoskeletal Proteins
  • Growth Substances
  • Insulin
  • Integrins
  • PXN protein, human
  • Paxillin
  • Phosphoproteins
  • Pxn protein, rat
  • Epidermal Growth Factor
  • Insulin-Like Growth Factor I
  • Nerve Growth Factor
  • ErbB Receptors
  • Protein-Tyrosine Kinases
  • Focal Adhesion Kinase 1
  • Focal Adhesion Kinase 2
  • Focal Adhesion Protein-Tyrosine Kinases
  • PTK2 protein, human
  • Ptk2 protein, rat
  • Ptk2b protein, rat
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases