Tyrosine phosphorylation of netrin receptors in netrin-1 signaling

Xiu Rong Ren, Yan Hong, Zhu Feng, Hong Mei Yang, Lin Mei, Wen Cheng Xiong

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Deleted in colorectal cancer (DCC) and neogenin are receptors of netrins, a family of guidance cues that promote axon outgrowth and guide growth cones in developing nervous system. The intracellular mechanisms of netrins, however, remain elusive. In this paper, we show that both DCC and neogenin become tyrosine phosphorylated in cortical neurons in response to netrin-1. Using a site-specific antiphosphor DCC antibody, we show that Y1420 phosphorylation is increased in netrin-1-stimulated neurons and that tyrosine-phosphorylated DCC is located in growth cones. In addition, we show that tyrosine-phosphorylated DCC selectively interacts with the Src family kinases Fyn and Lck, but not Src, c-Abl, Grb2, SHIP1, Shc, or tensin, suggesting a role of Fyn or Lck in netrin-1-DCC signaling. Of interest to note is that tyrosine-phosphorylated neogenin and uncoordinated 5 H2 (Unc5H2) not only bind to the Src homology 2 (SH2) domains of Fyn and SHP2, but also interact with the SH2 domain of SHIP1, suggesting a differential signaling between DCC and neogenin/Unc5H2. Furthermore, we demonstrate that inhibition of Src family kinase activity attenuated netrin-1-induced neurite outgrowth. Together, these results suggest a role of Src family kinases and tyrosine phosphorylation of netrin-1 receptors in regulating netrin-1 function.

Original languageEnglish (US)
Pages (from-to)235-245
Number of pages11
JournalNeuroSignals
Volume16
Issue number2-3
DOIs
StatePublished - Feb 1 2008

Fingerprint

Tyrosine
Colorectal Neoplasms
Phosphorylation
src-Family Kinases
Growth Cones
src Homology Domains
Neurons
netrin-1
netrin receptors
Nervous System
Cues
neogenin
Antibodies

Keywords

  • Deleted in colorectal cancer
  • Focal adhesion kinase
  • Fyn
  • Neogenin
  • Netrin-1

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience
  • Cellular and Molecular Neuroscience

Cite this

Ren, X. R., Hong, Y., Feng, Z., Yang, H. M., Mei, L., & Xiong, W. C. (2008). Tyrosine phosphorylation of netrin receptors in netrin-1 signaling. NeuroSignals, 16(2-3), 235-245. https://doi.org/10.1159/000111566

Tyrosine phosphorylation of netrin receptors in netrin-1 signaling. / Ren, Xiu Rong; Hong, Yan; Feng, Zhu; Yang, Hong Mei; Mei, Lin; Xiong, Wen Cheng.

In: NeuroSignals, Vol. 16, No. 2-3, 01.02.2008, p. 235-245.

Research output: Contribution to journalArticle

Ren, XR, Hong, Y, Feng, Z, Yang, HM, Mei, L & Xiong, WC 2008, 'Tyrosine phosphorylation of netrin receptors in netrin-1 signaling', NeuroSignals, vol. 16, no. 2-3, pp. 235-245. https://doi.org/10.1159/000111566
Ren XR, Hong Y, Feng Z, Yang HM, Mei L, Xiong WC. Tyrosine phosphorylation of netrin receptors in netrin-1 signaling. NeuroSignals. 2008 Feb 1;16(2-3):235-245. https://doi.org/10.1159/000111566
Ren, Xiu Rong ; Hong, Yan ; Feng, Zhu ; Yang, Hong Mei ; Mei, Lin ; Xiong, Wen Cheng. / Tyrosine phosphorylation of netrin receptors in netrin-1 signaling. In: NeuroSignals. 2008 ; Vol. 16, No. 2-3. pp. 235-245.
@article{4e8aba5e6c3d4710bca28cceaa7dab07,
title = "Tyrosine phosphorylation of netrin receptors in netrin-1 signaling",
abstract = "Deleted in colorectal cancer (DCC) and neogenin are receptors of netrins, a family of guidance cues that promote axon outgrowth and guide growth cones in developing nervous system. The intracellular mechanisms of netrins, however, remain elusive. In this paper, we show that both DCC and neogenin become tyrosine phosphorylated in cortical neurons in response to netrin-1. Using a site-specific antiphosphor DCC antibody, we show that Y1420 phosphorylation is increased in netrin-1-stimulated neurons and that tyrosine-phosphorylated DCC is located in growth cones. In addition, we show that tyrosine-phosphorylated DCC selectively interacts with the Src family kinases Fyn and Lck, but not Src, c-Abl, Grb2, SHIP1, Shc, or tensin, suggesting a role of Fyn or Lck in netrin-1-DCC signaling. Of interest to note is that tyrosine-phosphorylated neogenin and uncoordinated 5 H2 (Unc5H2) not only bind to the Src homology 2 (SH2) domains of Fyn and SHP2, but also interact with the SH2 domain of SHIP1, suggesting a differential signaling between DCC and neogenin/Unc5H2. Furthermore, we demonstrate that inhibition of Src family kinase activity attenuated netrin-1-induced neurite outgrowth. Together, these results suggest a role of Src family kinases and tyrosine phosphorylation of netrin-1 receptors in regulating netrin-1 function.",
keywords = "Deleted in colorectal cancer, Focal adhesion kinase, Fyn, Neogenin, Netrin-1",
author = "Ren, {Xiu Rong} and Yan Hong and Zhu Feng and Yang, {Hong Mei} and Lin Mei and Xiong, {Wen Cheng}",
year = "2008",
month = "2",
day = "1",
doi = "10.1159/000111566",
language = "English (US)",
volume = "16",
pages = "235--245",
journal = "Neuro-Signals",
issn = "1424-862X",
publisher = "S. Karger AG",
number = "2-3",

}

TY - JOUR

T1 - Tyrosine phosphorylation of netrin receptors in netrin-1 signaling

AU - Ren, Xiu Rong

AU - Hong, Yan

AU - Feng, Zhu

AU - Yang, Hong Mei

AU - Mei, Lin

AU - Xiong, Wen Cheng

PY - 2008/2/1

Y1 - 2008/2/1

N2 - Deleted in colorectal cancer (DCC) and neogenin are receptors of netrins, a family of guidance cues that promote axon outgrowth and guide growth cones in developing nervous system. The intracellular mechanisms of netrins, however, remain elusive. In this paper, we show that both DCC and neogenin become tyrosine phosphorylated in cortical neurons in response to netrin-1. Using a site-specific antiphosphor DCC antibody, we show that Y1420 phosphorylation is increased in netrin-1-stimulated neurons and that tyrosine-phosphorylated DCC is located in growth cones. In addition, we show that tyrosine-phosphorylated DCC selectively interacts with the Src family kinases Fyn and Lck, but not Src, c-Abl, Grb2, SHIP1, Shc, or tensin, suggesting a role of Fyn or Lck in netrin-1-DCC signaling. Of interest to note is that tyrosine-phosphorylated neogenin and uncoordinated 5 H2 (Unc5H2) not only bind to the Src homology 2 (SH2) domains of Fyn and SHP2, but also interact with the SH2 domain of SHIP1, suggesting a differential signaling between DCC and neogenin/Unc5H2. Furthermore, we demonstrate that inhibition of Src family kinase activity attenuated netrin-1-induced neurite outgrowth. Together, these results suggest a role of Src family kinases and tyrosine phosphorylation of netrin-1 receptors in regulating netrin-1 function.

AB - Deleted in colorectal cancer (DCC) and neogenin are receptors of netrins, a family of guidance cues that promote axon outgrowth and guide growth cones in developing nervous system. The intracellular mechanisms of netrins, however, remain elusive. In this paper, we show that both DCC and neogenin become tyrosine phosphorylated in cortical neurons in response to netrin-1. Using a site-specific antiphosphor DCC antibody, we show that Y1420 phosphorylation is increased in netrin-1-stimulated neurons and that tyrosine-phosphorylated DCC is located in growth cones. In addition, we show that tyrosine-phosphorylated DCC selectively interacts with the Src family kinases Fyn and Lck, but not Src, c-Abl, Grb2, SHIP1, Shc, or tensin, suggesting a role of Fyn or Lck in netrin-1-DCC signaling. Of interest to note is that tyrosine-phosphorylated neogenin and uncoordinated 5 H2 (Unc5H2) not only bind to the Src homology 2 (SH2) domains of Fyn and SHP2, but also interact with the SH2 domain of SHIP1, suggesting a differential signaling between DCC and neogenin/Unc5H2. Furthermore, we demonstrate that inhibition of Src family kinase activity attenuated netrin-1-induced neurite outgrowth. Together, these results suggest a role of Src family kinases and tyrosine phosphorylation of netrin-1 receptors in regulating netrin-1 function.

KW - Deleted in colorectal cancer

KW - Focal adhesion kinase

KW - Fyn

KW - Neogenin

KW - Netrin-1

UR - http://www.scopus.com/inward/record.url?scp=39349108018&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=39349108018&partnerID=8YFLogxK

U2 - 10.1159/000111566

DO - 10.1159/000111566

M3 - Article

C2 - 18253061

AN - SCOPUS:39349108018

VL - 16

SP - 235

EP - 245

JO - Neuro-Signals

JF - Neuro-Signals

SN - 1424-862X

IS - 2-3

ER -