Tyrosine phosphorylated Disabled 1 recruits Crk family adapter proteins

Yongcheng Huang; Susan Magdaleno; Rachel Hopkins; Clive Slaughter; Tom Curran; Lakhu Keshvara

doi:10.1016/j.bbrc.2004.04.023

Tyrosine phosphorylated Disabled 1 recruits Crk family adapter proteins

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

Research output: Contribution to journal › Article › peer-review

65 Scopus citations

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 language	English (US)
Pages (from-to)	204-212
Number of pages	9
Journal	Biochemical and Biophysical Research Communications
Volume	318
Issue number	1
DOIs	https://doi.org/10.1016/j.bbrc.2004.04.023
State	Published - May 21 2004
Externally published	Yes

Keywords

Crk
Dab1
MALDI-TOF
Reelin
SH2
Src
Tyrosine phosphorylation

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2004.04.023

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title = "Tyrosine phosphorylated Disabled 1 recruits Crk family adapter proteins",

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.",

keywords = "Crk, Dab1, MALDI-TOF, Reelin, SH2, Src, Tyrosine phosphorylation",

author = "Yongcheng Huang and Susan Magdaleno and Rachel Hopkins and Clive Slaughter and Tom Curran and Lakhu Keshvara",

note = "Funding Information: We thank Drs. Joan Brugge, Sansana Sawasdikosol, Lawrence Quillium, and John Groffen for valuable reagents. We are also thankful to Ashutosh Mishra and Rohan Keshwara for technical help. This work was supported in part by National Institute of Health/National Institute of Neurological Disorders and Stroke Grant RO1-NS36558 (T.C.). The authors also acknowledge the support of the American Lebanese Syrian Associated Charities (ALSAC).",

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doi = "10.1016/j.bbrc.2004.04.023",

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T1 - Tyrosine phosphorylated Disabled 1 recruits Crk family adapter proteins

AU - Huang, Yongcheng

AU - Magdaleno, Susan

AU - Hopkins, Rachel

AU - Slaughter, Clive

AU - Curran, Tom

AU - Keshvara, Lakhu

N1 - Funding Information: We thank Drs. Joan Brugge, Sansana Sawasdikosol, Lawrence Quillium, and John Groffen for valuable reagents. We are also thankful to Ashutosh Mishra and Rohan Keshwara for technical help. This work was supported in part by National Institute of Health/National Institute of Neurological Disorders and Stroke Grant RO1-NS36558 (T.C.). The authors also acknowledge the support of the American Lebanese Syrian Associated Charities (ALSAC).

PY - 2004/5/21

Y1 - 2004/5/21

N2 - 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.

AB - 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.

KW - Crk

KW - Dab1

KW - MALDI-TOF

KW - Reelin

KW - SH2

KW - Src

KW - Tyrosine phosphorylation

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Tyrosine phosphorylated Disabled 1 recruits Crk family adapter proteins

Abstract

Keywords

ASJC Scopus subject areas

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