RGD Reference Report - Cytosolic adaptor protein Dab2 is an intracellular ligand of endocytic receptor gp600/megalin. - Rat Genome Database

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Cytosolic adaptor protein Dab2 is an intracellular ligand of endocytic receptor gp600/megalin.

Authors: Oleinikov, AV  Zhao, J  Makker, SP 
Citation: Oleinikov AV, etal., Biochem J. 2000 May 1;347 Pt 3:613-21.
RGD ID: 7243160
Pubmed: PMID:10769163   (View Abstract at PubMed)
PMCID: PMC1220996   (View Article at PubMed Central)

gp600/megalin, an endocytic receptor, belongs to the low-density lipoprotein receptor family. It is most abundant in the renal proximal tubular cells, where it is implicated in the reabsorption of a number of molecules filtered through the glomerulus. The cytoplasmic tail (CT) of gp600/megalin contains a number of sequence similarities, which indicate that gp600/megalin might be involved in signal transduction. To find intracellular proteins that would interact with the gp600/megalin CT, a human kidney cDNA library was screened by using the yeast two-hybrid system. The phosphotyrosine interaction domain (PID) of the Disabled protein 2 (Dab2), a mammalian structural analogue of Drosophila Disabled, was found to bind to the gp600/megalin CT in this system. The interaction between these two proteins was confirmed by a binding assay in vitro and by the co-immunoprecipitation of both proteins from renal cell lysates. The gp600/megalin CT contains three PsiXNPXY motifs (in which Psi represents a hydrophobic residue) that are potentially able to interact with PID. Analysis of the CT deletion and point-mutation variants of gp600/megalin by the two-hybrid system revealed that the third PsiXNPXY motif is most probably involved in this interaction. Dab2 is a mitogen-responsive phosphoprotein thought to be an adaptor molecule involved in signal transduction, and a suggested negative regulator of cell growth. Dab2 is the first intracellular ligand identified for gp600/megalin; gp600/megalin is the first known transmembrane receptor that interacts with the cytosolic protein Dab2. We speculate that their interaction might involve gp600/megalin in signal transduction pathways or might mediate the intracellular trafficking of this receptor.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein binding enablesIPIUniProtKB:P981587243160PMID:10769163IntAct 
protein binding enablesIPIUniProtKB:O887977243160PMID:10769163IntAct 

Objects Annotated

Genes (Rattus norvegicus)
Dab2  (DAB adaptor protein 2)
Lrp2  (LDL receptor related protein 2)


Additional Information