Gene interactions and pathways from curated databases and text-mining
Nat Neurosci 2008, PMID: 18066058

Netrin signal transduction and the guanine nucleotide exchange factor DOCK180 in attractive signaling.

Li, Xiaoling; Gao, Xue; Liu, Guofa; Xiong, Wencheng; Wu, Jane; Rao, Yi

Netrins are prototypical axon guidance cues whose attractive signaling requires the small GTPase Rac1. It remains unclear how Rac1 is regulated in the netrin pathway. DOCK180 is a member of a new family of guanine nucleotide exchange factors for Rho GTPases. Here we provide evidence implicating DOCK180 in netrin signal transduction. Netrin promoted the formation of a protein-protein interaction complex that included DOCK180 and the netrin receptor deleted in colorectal carcinoma (DCC). Inhibition of DOCK180 reduced activation of Rac1 by netrin. Both axon outgrowth and axon attraction induced by netrin were inhibited after DOCK180 knockdown in vertebrate neurons. The in vivo functional role of DOCK180 was demonstrated by its requirement for projection of commissural axons in the neural tube. These findings indicate that netrin stimulation recruits DOCK180 through DCC, which then activates small GTPases, suggesting an essential role for DOCK180 in mediating attractive responses by neurons to netrin-1.

Diseases/Pathways annotated by Medline MESH: Colorectal Neoplasms
Document information provided by NCBI PubMed

Text Mining Data

Rac1 → DOCK180: " Inhibition of DOCK180 reduced activation of Rac1 by netrin "

DOCK180 → netrin-1: " These findings indicate that netrin stimulation recruits DOCK180 through DCC, which then activates small GTPases, suggesting an essential role for DOCK180 in mediating attractive responses by neurons to netrin-1 "

Manually curated Databases

  • NCI Pathway Database Netrin-mediated signaling events: netrin 1/DCC complex (NTN1-DCC) → DOCK1/ELMO1 complex (DOCK1-ELMO1) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database Netrin-mediated signaling events: netrin 1/DCC complex (NTN1-DCC) → netrin 1/DCC/DOCK1/ELMO1 complex (NTN1-DCC-DOCK1-ELMO1) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database Netrin-mediated signaling events: DOCK1/ELMO1 complex (DOCK1-ELMO1) → netrin 1/DCC/DOCK1/ELMO1 complex (NTN1-DCC-DOCK1-ELMO1) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database Netrin-mediated signaling events: None → RAC1/GDP complex (RAC1) (modification, collaborate)
    Evidence: mutant phenotype, assay
  • NCI Pathway Database Netrin-mediated signaling events: None → RAC1/GTP complex (RAC1) (modification, collaborate)
    Evidence: mutant phenotype, assay
  • NCI Pathway Database Netrin-mediated signaling events: None → netrin 1/DCC/DOCK1/ELMO1 complex (NTN1-DCC-DOCK1-ELMO1) (modification, collaborate)
    Evidence: mutant phenotype, assay
  • NCI Pathway Database Netrin-mediated signaling events: None → None (modification, collaborate)
    Evidence: mutant phenotype, assay
  • NCI Pathway Database Netrin-mediated signaling events: RAC1/GDP complex (RAC1) → RAC1/GTP complex (RAC1) (modification, collaborate)
    Evidence: mutant phenotype, assay
  • NCI Pathway Database Netrin-mediated signaling events: RAC1/GDP complex (RAC1) → netrin 1/DCC/DOCK1/ELMO1 complex (NTN1-DCC-DOCK1-ELMO1) (modification, collaborate)
    Evidence: mutant phenotype, assay
  • NCI Pathway Database Netrin-mediated signaling events: RAC1/GDP complex (RAC1) → None (modification, collaborate)
    Evidence: mutant phenotype, assay
  • NCI Pathway Database Netrin-mediated signaling events: RAC1/GTP complex (RAC1) → None (modification, collaborate)
    Evidence: mutant phenotype, assay
  • NCI Pathway Database Netrin-mediated signaling events: netrin 1/DCC/DOCK1/ELMO1 complex (NTN1-DCC-DOCK1-ELMO1) → None (modification, activates)
    Evidence: mutant phenotype, assay
  • Reactome Reaction: PTK2 → TRIO (reaction)
  • Reactome Reaction: NCK1 → NTN1 (reaction)
  • Reactome Reaction: TRIO → TRIO (reaction)
  • Reactome Reaction: PTK2 → NTN1 (reaction)
  • Reactome Reaction: NCK1 → SRC (reaction)
  • Reactome Reaction: NTN1 → SRC (reaction)
  • Reactome Reaction: PTK2 → FYN (reaction)
  • Reactome Reaction: NCK1 → NCK1 (reaction)
  • Reactome Reaction: NCK1 → RAC1 (reaction)
  • Reactome Reaction: FYN → DOCK1 (indirect_complex)
  • Reactome Reaction: SRC → TRIO (reaction)
  • Reactome Reaction: PTK2 → DOCK1 (indirect_complex)
  • Reactome Reaction: PTK2 → RAC1 (reaction)
  • Reactome Reaction: PTK2 → PTK2 (reaction)
  • Reactome Reaction: DCC → TRIO (reaction)
  • Reactome Reaction: NTN1 → RAC1 (indirect_complex)
  • Reactome Reaction: PTK2 → SRC (reaction)
  • Reactome Reaction: FYN → TRIO (reaction)
  • Reactome Reaction: NTN1 → NTN1 (reaction)
  • Reactome Reaction: DCC → DOCK1 (indirect_complex)
  • Reactome Reaction: DOCK1 → DOCK1 (reaction)
  • Reactome Reaction: DCC → NCK1 (reaction)
  • Reactome Reaction: NCK1 → RAC1 (indirect_complex)
  • Reactome Reaction: NCK1 → DOCK1 (indirect_complex)
  • Reactome Reaction: DCC → NTN1 (reaction)
  • Reactome Reaction: FYN → RAC1 (indirect_complex)
  • Reactome Reaction: NCK1 → TRIO (indirect_complex)
  • Reactome Reaction: NCK1 → DOCK1 (reaction)
  • Reactome Reaction: FYN → RAC1 (reaction)
  • Reactome Reaction: NTN1 → TRIO (reaction)
  • Reactome Reaction: PTK2 → DOCK1 (reaction)
  • Reactome Reaction: DOCK1 → TRIO (reaction)
  • Reactome Reaction: DOCK1 → RAC1 (indirect_complex)
  • Reactome Reaction: DCC → DOCK1 (reaction)
  • Reactome Reaction: DCC → RAC1 (reaction)
  • Reactome Reaction: DCC → FYN (reaction)
  • Reactome Reaction: FYN → DOCK1 (reaction)
  • Reactome Reaction: DCC → TRIO (indirect_complex)
  • Reactome Reaction: NTN1 → DOCK1 (indirect_complex)
  • Reactome Reaction: SRC → SRC (reaction)
  • Reactome Reaction: FYN → NCK1 (reaction)
  • Reactome Reaction: DCC → RAC1 (indirect_complex)
  • Reactome Reaction: FYN → TRIO (indirect_complex)
  • Reactome Reaction: FYN → NTN1 (reaction)
  • Reactome Reaction: NTN1 → TRIO (indirect_complex)
  • Reactome Reaction: FYN → FYN (reaction)
  • Reactome Reaction: DCC → PTK2 (reaction)
  • Reactome Reaction: PTK2 → RAC1 (indirect_complex)
  • Reactome Reaction: DCC → SRC (reaction)
  • Reactome Reaction: SRC → RAC1 (reaction)
  • Reactome Reaction: PTK2 → NCK1 (reaction)
  • Reactome Reaction: FYN → SRC (reaction)
  • Reactome Reaction: TRIO → RAC1 (reaction)
  • Reactome Reaction: SRC → DOCK1 (indirect_complex)
  • Reactome Reaction: NCK1 → TRIO (reaction)
  • Reactome Reaction: DCC → DCC (reaction)
  • Reactome Reaction: SRC → RAC1 (indirect_complex)
  • Reactome Reaction: SRC → TRIO (indirect_complex)
  • Reactome Reaction: TRIO → RAC1 (indirect_complex)
  • Reactome Reaction: DOCK1 → RAC1 (reaction)
  • Reactome Reaction: NTN1 → DOCK1 (reaction)
  • Reactome Reaction: SRC → DOCK1 (reaction)
  • Reactome Reaction: NTN1 → RAC1 (reaction)
  • Reactome Reaction: PTK2 → TRIO (indirect_complex)
In total, 50 gene pairs are associated to this article in curated databases