Tyrosine phosphorylated Disabled 1 recruits Crk family adapter proteins

Yongcheng Huang, Susan Magdaleno, Rachel Hopkins, Clive A. Slaughter, Tom Curran, Lakhu Keshvara

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Disabled 1 (Dab1) functions as a critical adapter protein in the Reelin signaling pathway to direct proper positioning of neurons during brain development. Reelin stimulates phosphorylation of Dab1 on tyrosines 198 and 220, and phosphorylated Dab1 is likely to interact with downstream signaling proteins that contain Src homology 2 (SH2) domains. To search for such proteins, we used a Sepharose-conjugated peptide containing phosphotyrosine 220 (PTyr-220) of Dab1, as an affinity matrix to capture binding proteins from mouse brain extracts. Mass spectrometric analysis of bound proteins revealed that Crk family adapter proteins selectively associated with this phosphorylation site. We further show that Crk-I and Crk-II, but not CrkL, stimulate phosphorylation of Dab1 on tyrosine 220 in a Src-dependent manner. Our results suggest that Crk family adapter proteins may play an important role in the Reelin signaling pathway during brain development.

Original languageEnglish (US)
Pages (from-to)204-212
Number of pages9
JournalBiochemical and Biophysical Research Communications
Volume318
Issue number1
DOIs
StatePublished - May 21 2004
Externally publishedYes

Fingerprint

Tyrosine
Phosphorylation
Brain
Proteins
Phosphotyrosine
src Homology Domains
Sepharose
Carrier Proteins
Neurons
Peptides

Keywords

  • Crk
  • Dab1
  • MALDI-TOF
  • Reelin
  • SH2
  • Src
  • Tyrosine phosphorylation

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Tyrosine phosphorylated Disabled 1 recruits Crk family adapter proteins. / Huang, Yongcheng; Magdaleno, Susan; Hopkins, Rachel; Slaughter, Clive A.; Curran, Tom; Keshvara, Lakhu.

In: Biochemical and Biophysical Research Communications, Vol. 318, No. 1, 21.05.2004, p. 204-212.

Research output: Contribution to journalArticle

Huang, Yongcheng ; Magdaleno, Susan ; Hopkins, Rachel ; Slaughter, Clive A. ; Curran, Tom ; Keshvara, Lakhu. / Tyrosine phosphorylated Disabled 1 recruits Crk family adapter proteins. In: Biochemical and Biophysical Research Communications. 2004 ; Vol. 318, No. 1. pp. 204-212.
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