Article abstract
Nature Cell Biology 2, 574 - 581 (2000)
Published online: 10 August 2000 | doi:10.1038/35023515
Pyk2 and FAK regulate neurite outgrowth induced by growth factors and integrins
Inga Ivankovic-Dikic1, Eva Grönroos1, Andree Blaukat1, Bernd-Uwe Barth1 & Ivan Dikic1
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.
- Ludwig Institute for Cancer Research, Box 595, Husargatan 3, Uppsala, S- 75124, Sweden
Correspondence to: Ivan Dikic1 e-mail: Ivan.Dikic@licr.uu.se
