c-Abl phosphorylates Dok1 to promote filopodia during cell spreading Journal Article
| Authors: | Woodring, P. J.; Meisenhelder, J.; Johnson, S. A.; Zhou, G. L.; Field, J.; Shah, K.; Bladt, F.; Pawson, T.; Niki, M.; Pandolfi, P. P.; Wang, J. Y. J.; Hunter, T. |
| Article Title: | c-Abl phosphorylates Dok1 to promote filopodia during cell spreading |
| 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. |
| Keywords: | signal transduction; controlled study; protein phosphorylation; unclassified drug; dna-binding proteins; nonhuman; protein localization; animal cell; mouse; animals; mice; embryo; protein; abelson kinase; tyrosine; phosphorylation; animalia; rna-binding proteins; gene disruption; oncogene proteins; cell migration; fibroblast; fibroblasts; cell movement; cell line, transformed; phosphoproteins; protein structure, tertiary; protein structure; f actin; actins; cell activation; cell adhesion; actin polymerization; cytoskeleton; protein cdc42; filopodium; fibronectin; adaptor protein; proto-oncogene proteins c-abl; pseudopodia; cell spreading; nck; priority journal; article; abl-/-arg-/- fibroblasts; f-actin microspikes; fibronectin adhesion; dok1 protein; nck protein; src homology 2 domain; src homology domain; src homology domains |
| Journal Title: | Journal of Cell Biology |
| Volume: | 165 |
| Issue: | 4 |
| ISSN: | 0021-9525 |
| Publisher: | Rockefeller University Press |
| Date Published: | 2004-05-17 |
| Start Page: | 493 |
| End Page: | 503 |
| Language: | English |
| DOI: | 10.1083/jcb.200312171 |
| PROVIDER: | scopus |
| PMCID: | PMC2172353 |
| PUBMED: | 15148308 |
| DOI/URL: | |
| Notes: | J. Cell Biol. -- Cited By (since 1996):46 -- Export Date: 16 June 2014 -- CODEN: JCLBA -- Source: Scopus |
