RGD Reference Report - Crosstalk between PSD-95 and JIP1-mediated signaling modules: the mechanism of MLK3 activation in cerebral ischemia. - Rat Genome Database

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Crosstalk between PSD-95 and JIP1-mediated signaling modules: the mechanism of MLK3 activation in cerebral ischemia.

Authors: Zhang, QX  Pei, DS  Guan, QH  Sun, YF  Liu, XM  Zhang, GY 
Citation: Zhang QX, etal., Biochemistry. 2007 Apr 3;46(13):4006-16. Epub 2007 Mar 10.
RGD ID: 2298766
Pubmed: PMID:17348686   (View Abstract at PubMed)
DOI: DOI:10.1021/bi0615386   (Journal Full-text)

Our previous study indicates that global ischemia facilitates the assembly of the GluR6.PSD-95.MLK3 signaling module, which in turn activated MLK3, leading to exacerbated ischemic neuron death. In addition, JIP1, functioning as a scaffold protein, could couple MLK3-MKK7-JNK to form a specific signaling module and facilitate the activation of the JNK signal pathway. However, the organization, regulation, and function between the two signaling modules and the effects they have on MLK3 activation remain incompletely understood. Here, we show that JIP1 maintains MLK3 in an inactive and monomeric state; once activated, MLK3 binds to PSD-95 and then dimerizes and autophosphorylates. In addition, a GluR6 C-terminus-containing peptide (Tat-GluR6-9c) and antisense oligonucleotides (AS-ODNs) against PSD-95 inhibit the integration of PSD-95 and MLK3 and the dimerization of MLK3, facilitate the interaction of JIP1 and MLK3, and, consequently, perform neuroprotection on neuron death. However, AS-ODNs against JIP1 play a negative role compared to that mentioned above. The findings show that the crosstalk occurs between PSD-95 and the JIP1-mediated signaling module, which may be involved in brain ischemic injury and contribute to the regulation of MLK3 activation. Thus, specific blockade of PSD-95-MLK3 coupling may reduce the extent of ischemia-reperfusion-induced neuronal cell death.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
regulation of JNK cascade  IMP 2298766 RGD 

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Map2k7  (mitogen activated protein kinase kinase 7)
Map3k11  (mitogen-activated protein kinase kinase kinase 11)
Mapk8  (mitogen-activated protein kinase 8)
Mapk8ip1  (mitogen-activated protein kinase 8 interacting protein 1)
Mapk9  (mitogen-activated protein kinase 9)


Additional Information