RGD Reference Report - Myelin suppresses axon regeneration by PIR-B/SHP-mediated inhibition of Trk activity. - Rat Genome Database

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Myelin suppresses axon regeneration by PIR-B/SHP-mediated inhibition of Trk activity.

Authors: Fujita, Y  Endo, S  Takai, T  Yamashita, T 
Citation: Fujita Y, etal., EMBO J. 2011 Apr 6;30(7):1389-401. doi: 10.1038/emboj.2011.55. Epub 2011 Mar 1.
RGD ID: 8554762
Pubmed: PMID:21364532   (View Abstract at PubMed)
PMCID: PMC3094118   (View Article at PubMed Central)
DOI: DOI:10.1038/emboj.2011.55   (Journal Full-text)

Paired immunoglobulin-like receptor B (PIR-B) partially mediates the regeneration-inhibiting effects of the myelin-derived protein Nogo, myelin-associated glycoprotein (MAG), and oligodendrocyte-myelin glycoprotein (OMgp). In this study, we report that inhibition of the PIR-B signaling cascades in neurons enhances axon regeneration in the central nervous system (CNS). Binding of MAG to PIR-B led to the association of PIR-B with tropomyosin receptor kinase (Trk) neurotrophin receptors. Src homology 2-containing protein tyrosine phosphatase (SHP)-1 and SHP-2, which were recruited to PIR-B upon MAG binding, functioned as Trk tyrosine phosphatases. Further, SHP-1 and SHP-2 inhibition reduced MAG-induced dephosphorylation of Trk receptors and abolished the inhibitory effect of MAG on neurite growth. Thus, PIR-B associated with Trk to downregulate basal and neurotrophin-regulated Trk activity through SHP-1/2 in neurons. Moreover, in vivo transfection of small interfering RNA (siRNA) for SHP-1 or SHP-2 induced axonal regeneration after optic nerve injury in mice. Our results thus identify a new molecular target to enhance regeneration of the injured CNS.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein binding enablesIPIUniProtKB:Q8K4V68554762PMID:21364532IntAct 

Objects Annotated

Genes (Rattus norvegicus)
Ntrk2  (neurotrophic receptor tyrosine kinase 2)


Additional Information