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pubmed:abstractText |
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.
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pubmed:affiliation |
Ludwig Institute for Cancer Research, Box 595, Husargatan 3, Uppsala, S- 75124, Sweden. Ivan.Dikic@licr.uu.se
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