Skip to main content
eScholarship
Open Access Publications from the University of California

c-Abl phosphorylates Dok1 to promote filopodia during cell spreading.

  • Author(s): Woodring, Pamela J
  • Meisenhelder, Jill
  • Johnson, Sam A
  • Zhou, Guo-Lei
  • Field, Jeffrey
  • Shah, Kavita
  • Bladt, Friedhelm
  • Pawson, Tony
  • Niki, Masaru
  • Pandolfi, Pier Paolo
  • Wang, Jean YJ
  • Hunter, Tony
  • et al.
Abstract

Filopodia are dynamic F-actin structures that cells use to explore their environment. c-Abl tyrosine kinase promotes filopodia during cell spreading through an unknown mechanism that does not require Cdc42 activity. Using an unbiased approach, we identified Dok1 as a specific c-Abl substrate in spreading fibroblasts. When activated by cell adhesion, c-Abl phosphorylates Y361 of Dok1, promoting its association with the Src homology 2 domain (SH2)/SH3 adaptor protein Nck. Each signaling component was critical for filopodia formation during cell spreading, as evidenced by the finding that mouse fibroblasts lacking c-Abl, Dok1, or Nck had fewer filopodia than cells reexpressing the product of the disrupted gene. Dok1 and c-Abl stimulated filopodia in a mutually interdependent manner, indicating that they function in the same signaling pathway. Dok1 and c-Abl were both detected in filopodia of spreading cells, and therefore may act locally to modulate actin. Our data suggest a novel pathway by which c-Abl transduces signals to the actin cytoskeleton through phosphorylating Dok1 Y361 and recruiting Nck.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content
Current View