Interaction between Dab1 and CrkII is promoted by Reelin signalling

Kelian Chen, Pawel G. Ochalski, Tracy S. Tran, Nadia Sahir, Manfred Schubert, Albéna Pramatarova, Brian W. Howell

Research output: Contribution to journalArticlepeer-review

77 Scopus citations


Reelin-induced Dab1 tyrosine phosphorylation has been implicated in the regulation of neuronal positioning during brain development. The downstream consequences of Dab1 tyrosine phosphorylation are not fully understood, however. Here we identify CrkII, CrkL and Dock1 in complexes bound to tyrosine-phosphorylated Dab1, through mass spectrometry. The CrkII-Dab1 interaction requires tyrosine phosphorylation of Dah1 at residues 220 or 232 and is promoted by Reelin treatment of embryonic forebrain neurons. Unlike other CrkII binding proteins, such as paxillin and p130Cas, expression of Dah1 interfered with CrkII-dependent cell migration of Nara Bladder Tumor II (NBT-II) cells, in a tyrosine phosphorylation-site dependent manner. Overexpression of CrkIIGFP rescued the migration of these cells, suggesting that Dah1 makes Crk a limiting factor for migration. The Dock1-Dab1 association is indirect and requires CrkII. In organisms such as Drosophila melanogaster and Caenorhabditis elegans, signaling complexes, which contain Crk and Dock1 family members are conserved and act through Rac. We show that a rough-eye phenotype in Drosophila caused by exogenous expression of tyrosine-phosphorylated mouse Dab1RFP is partially rescued by a loss-of-function mutation in myoblast city, a Dock1 -like gene in Drosophila. We propose a model that tyrosine-phosphorylated Dab1 engages the conserved Crk-Dock1-Rac signaling cassette, but when bound to Dah1 this signaling complex does not support migration.

Original languageEnglish (US)
Pages (from-to)4527-4536
Number of pages10
JournalJournal of cell science
Issue number19
StatePublished - Sep 1 2004
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cell Biology


  • Brain development
  • Crk
  • Dab1
  • Dock1
  • Reelin


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