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Published online 22 October 2001. doi:10.1083/jcb.200107063
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© The Rockefeller University Press, 0021-9525/2001/10/427 $5.00
The Journal of Cell Biology, Volume 155, Number 3, October 29, 2001 427-438

Article

 Transmission of growth cone traction force through apCAM–cytoskeletal linkages is regulated by Src family tyrosine kinase activity

Daniel M. Suter and Paul Forscher

Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520

Address correspondence to Dr. Paul Forscher, Department of Molecular, Cellular, and Developmental Biology, Yale University, P.O. Box 208103, New Haven, CT 06520-8103. Tel.: (203) 432-6344. Fax: (203) 432-6161. E-mail: paul.forscher{at}yale.edu

Tyrosine kinase activity is known to be important in neuronal growth cone guidance. However, underlying cellular mechanisms are largely unclear. Here, we report how Src family tyrosine kinase activity controls apCAM-mediated growth cone steering by regulating the transmission of traction forces through receptor–cytoskeletal linkages. Increased levels of tyrosine phosphorylation were detected at sites where beads coated with apCAM ligands were physically restrained to induce growth cone steering, but not at unrestrained bead binding sites. Interestingly, the rate and level of phosphotyrosine buildup near restrained beads were decreased by the myosin inhibitor 2,3-butanedione-2-monoxime, suggesting that tension promotes tyrosine kinase activation. While not affecting retrograde F-actin flow rates, genistein and the Src family selective tyrosine kinase inhibitors PP1 and PP2 strongly reduced the growth cone's ability to apply traction forces through apCAM–cytoskeletal linkages, assessed using the restrained bead interaction assay. Furthermore, increased levels of an activated Src family kinase were detected at restrained bead sites during growth cone steering events. Our results suggest a mechanism by which growth cones select pathways by sampling both the molecular nature of the substrate and its ability to withstand the application of traction forces.

Key Words: apCAM; Src family tyrosine kinase; tyrosine phosphorylation; receptor–cytoskeletal coupling; growth cone steering


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