RGD Reference Report - Evaluation of the role of Disabled-2 in nerve growth factor-mediated neurite outgrowth and cellular signalling. - Rat Genome Database

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Evaluation of the role of Disabled-2 in nerve growth factor-mediated neurite outgrowth and cellular signalling.

Authors: Huang, CH  Cheng, JC  Chen, JC  Tseng, CP 
Citation: Huang CH, etal., Cell Signal. 2007 Jun;19(6):1339-47. Epub 2007 Jan 24.
RGD ID: 7243246
Pubmed: PMID:17317100   (View Abstract at PubMed)
DOI: DOI:10.1016/j.cellsig.2007.01.019   (Journal Full-text)

Disabled-2 (DAB2) is an adapter protein that plays a key role in cell proliferation and differentiation. We reported here that DAB2 is expressed in various regions of rat central nervous system and is most abundant in the olfactory bulb. The up-regulation of DAB2 upon 5,7-dihydroxytryptamine-induced spinal cord lesion implicates that DAB2 may participate in the regulation of neuronal plasticity. To investigate DAB2 function in the regulation of neurite outgrowth, the rat p59 and p82 form of DAB2 was individually and stably expressed in the PC12 cells. Both p59 and p82 inhibited nerve growth factor (NGF)-induced neurite outgrowth concomitantly with a decrease in the expression of neuron-specific cytoskeleton protein beta-tubulin III. To unveil the molecular mechanism of DAB2 in NGF signaling, we found that RhoA-GTPase activity was up-regulated in DAB2 stable lines whereas the Ras/MAPK and PI3-kinase/Akt signaling was not affected. The inhibitory effect of DAB2 on NGF-mediated neurite outgrowth was reversed by the pretreatment of Rho-kinase (ROCK) inhibitor Y27632, implicating that DAB2 modulates RhoA/ROCK signaling. Together, this study defines a role of DAB2 in the control of neuronal plasticity and demonstrates for the first time that DAB2 is a negative regulator in NGF-mediated neurite outgrowth.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Spinal Cord Injuries  IEP 7243246protein:increased expression:spinal cordRGD 
Spinal Cord Injuries  ISODab2 (Rattus norvegicus)7243246protein:increased expression:spinal cordRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of neuron projection development  IDA 7243246 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Dab2  (DAB adaptor protein 2)

Genes (Mus musculus)
Dab2  (disabled 2, mitogen-responsive phosphoprotein)


Additional Information