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The multi-PDZ domain protein MUPP1 is a cytoplasmic ligand for the membrane-spanning proteoglycan NG2.

http://www.ncbi.nlm.nih.gov/pubmed/10967549

A yeast two-hybrid screen was employed to identify ligands for the cytoplasmic domain of the NG2 chondroitin sulfate proteoglycan. Two overlapping cDNA clones selected in the screen are identical in sequence to a DNA segment coding for the most amino-terminal of the 13 PDZ domains found in the multi-PDZ-protein MUPP1. Antibodies made against recombinant polypeptides representing these two clones (NIP-2 and NIP-7) are reactive with the same 250-kDa molecule recognized by anti-MUPP1 antibodies, confirming the presence of the NIP-2 and NIP-7 sequences in the MUPP1 protein. NIP-2 and NIP-7 GST fusion proteins effectively recognize NG2 in pull-down assays, demonstrating the ability of these polypeptide segments to interact with the intact proteoglycan. The fusion proteins fail to bind NG2 missing the C-terminal half of the cytoplasmic domain, emphasizing the role of the NG2 C-terminus in the interaction with MUPP1. The existence of an NG2/MUPP1 interaction in situ is demonstrated by the ability of NG2 antibodies to co-immunoprecipitate both NG2 and MUPP1 from detergent extracts of cells expressing the two molecules. MUPP1 may serve as a multivalent scaffold that provides a means of linking NG2 with key structural and/or signaling components in the cytoplasm.

Pubmed ID: 10967549 RIS Download

Mesh terms: Amino Acid Sequence | Antigens | Base Sequence | Carrier Proteins | Cell Membrane | Cytoplasm | DNA, Complementary | Humans | Ligands | Molecular Sequence Data | Precipitin Tests | Proteoglycans | Sequence Homology, Nucleic Acid | Signal Transduction | Tumor Cells, Cultured

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Associated grants

  • Agency: NICHD NIH HHS, Id: P01 HD25938
  • Agency: NIAMS NIH HHS, Id: R01 AR44400
  • Agency: NCI NIH HHS, Id: R01 CA058541
  • Agency: NINDS NIH HHS, Id: R01 NS21990

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