| First Author | Woodring PJ | Year | 2004 |
| Journal | J Cell Biol | Volume | 165 |
| Issue | 4 | Pages | 493-503 |
| PubMed ID | 15148308 | Mgi Jnum | J:91138 |
| Mgi Id | MGI:3046013 | Doi | 10.1083/jcb.200312171 |
| Citation | Woodring PJ, et al. (2004) c-Abl phosphorylates Dok1 to promote filopodia during cell spreading. J Cell Biol 165(4):493-503 |
| abstractText | 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. |
