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PMID:23954828

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Citation

Pan, Y, Zhang, J, Liu, W, Shu, P, Yin, B, Yuan, J, Qiang, B and Peng, X (2013) Dok5 is involved in the signaling pathway of neurotrophin-3 against TrkC-induced apoptosis. Neurosci. Lett. 553:46-51

Abstract

TrkC is a dependence receptor and many reports have shown that neurotrophin-3 promotes cell survival by inhibiting TrkC-induced apoptosis in many cell lines. However, the identity of the adaptor protein involved in the NT-3/TrkC signaling pathway regulating cell death and survival remains unclear. The downstream of tyrosine kinase/docking protein (Dok) adaptor protein 5 is one substrate of the TrkC receptor. Because NT-3 and its receptor, TrkC, are strongly expressed by sensory neurons, we measured the expression of Dok5 and TrkC in the developing mouse spinal cord and dorsal root ganglia (DRG). We found that the number of cells positive for both Dok5 and TrkC decreases with DRG development. Immunoprecipitation and immunofluorescence staining showed that Dok5 interacted with TrkC and partially colocalized with TrkC in DRG neurons. In HEK293T cells, TrkC triggered apoptosis, but NT-3 prevented TrkC-induced apoptosis. Interestingly, siRNA knockdown of Dok5 expression partially prevented the protection of NT-3 against TrkC-induced apoptosis by regulating the activity of caspase-3. Taken together, we concluded that Dok5 is necessary for NT-3 signaling to block TrkC-induced apoptosis.

Links

PubMed Online version:10.1016/j.neulet.2013.08.006

Keywords

Adaptor Proteins, Signal Transducing/genetics; Adaptor Proteins, Signal Transducing/metabolism; Animals; Apoptosis; Caspase 3/metabolism; Embryo, Mammalian; Ganglia, Spinal/cytology; Ganglia, Spinal/embryology; Ganglia, Spinal/metabolism; Gene Knockdown Techniques; HEK293 Cells; Humans; Mice, Inbred ICR; Neurotrophin 3/metabolism; Phosphoproteins/genetics; Phosphoproteins/metabolism; Receptor, trkC/metabolism; Sensory Receptor Cells/metabolism; Signal Transduction

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:NTF3

acts_upstream_of_or_within

GO:0042981: regulation of apoptotic process

ECO:0000266: sequence orthology evidence used in manual assertion

UniProtKB:P20783

P

Seeded From UniProt

complete

HUMAN:NTF3

acts_upstream_of_or_within

GO:0042981: regulation of apoptotic process

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q6VNS1

P

Seeded From UniProt

complete

HUMAN:CASP3

acts_upstream_of_or_within

GO:0048011: neurotrophin TRK receptor signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:NTRK3

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q91ZM9

F

Seeded From UniProt

complete

MOUSE:NTRK3

acts_upstream_of_or_within

GO:0043065: positive regulation of apoptotic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:DOK5

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q6VNS1

F

Seeded From UniProt

complete

MOUSE:DOK5

acts_upstream_of_or_within

GO:0051386: regulation of neurotrophin TRK receptor signaling pathway

ECO:0000266: sequence orthology evidence used in manual assertion

UniProtKB:Q9P104

P

Seeded From UniProt

complete

HUMAN:DOK5

acts_upstream_of_or_within

GO:0051386: regulation of neurotrophin TRK receptor signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CASP3

involved_in

GO:0048011: neurotrophin TRK receptor signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:CASP3

acts_upstream_of_or_within

GO:0048011: neurotrophin TRK receptor signaling pathway

ECO:0000266: sequence orthology evidence used in manual assertion

UniProtKB:P42574

P

Seeded From UniProt

complete

Notes

See also

References

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