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

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.
Mesh Terms:
Animals, Cytoskeletal Proteins, Enzyme Activation, Epidermal Growth Factor, Focal Adhesion Kinase 1, Focal Adhesion Kinase 2, Focal Adhesion Protein-Tyrosine Kinases, Growth Substances, Humans, Insulin, Insulin-Like Growth Factor I, Integrins, Mitogen-Activated Protein Kinase 3, Mitogen-Activated Protein Kinases, Nerve Growth Factor, Neurites, PC12 Cells, Paxillin, Phosphoproteins, Protein-Tyrosine Kinases, Rats, Receptor, Epidermal Growth Factor, Signal Transduction, Tumor Cells, Cultured
Nat. Cell Biol.
Date: Sep. 01, 2000
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