RGD Reference Report - ProSAP/Shank postsynaptic density proteins interact with insulin receptor tyrosine kinase substrate IRSp53. - Rat Genome Database

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ProSAP/Shank postsynaptic density proteins interact with insulin receptor tyrosine kinase substrate IRSp53.

Authors: Bockmann, J  Kreutz, M R  Gundelfinger, E D  Böckers, T M 
Citation: Bockmann J, etal., J Neurochem. 2002 Nov;83(4):1013-7.
RGD ID: 11576289
Pubmed: PMID:12421375   (View Abstract at PubMed)

The ProSAP/Shank family of multidomain proteins of the postsynaptic density (PSD) can either directly or indirectly interact with NMDA-type and metabotropic glutamate receptors and the actin-based cytoskeleton. In a yeast two hybrid screen utilizing a proline-rich domain that is highly conserved among the ProSAP/Shank family members, we isolated several cDNA clones coding for the insulin receptor substrate IRSp53. The specificity of this interaction was confirmed in transfected COS cells. Co-immunoprecipitation of IRSp53 and ProSAP2 solubilized from rat brain membranes indicates that the interaction occurs in vivo. The C-terminal SH3 domain of IRSp53 is responsible for the interaction with a novel proline-rich consensus sequence of ProSAP/Shank that was characterized by mutational analysis. IRSp53 is a substrate for the insulin receptor in the brain and acts downstream of small GTPases of the Rho family. Binding of Cdc42Hs to IRSp53 induces actin filament assembly, reorganization and filopodia outgrowth in neuronal cell lines. Our data suggest that IRSp53 can be recruited to the PSD via its ProSAP/Shank interaction and may contribute to the morphological reorganization of spines and synapses after insulin receptor and/or Cdc42Hs activation.



Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Shank3Ratprotein binding  IPIBaiap2 (Rattus norvegicus) RGD 
Baiap2Ratscaffold protein binding  IPIShank3 (Rattus norvegicus) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Baiap2  (BAR/IMD domain containing adaptor protein 2)
Shank3  (SH3 and multiple ankyrin repeat domains 3)


Additional Information