Document Detail

The disabled 1 phosphotyrosine-binding domain binds to the internalization signals of transmembrane glycoproteins and to phospholipids.
MedLine Citation:
PMID:  10373567     Owner:  NLM     Status:  MEDLINE    
Disabled gene products are important for nervous system development in drosophila and mammals. In mice, the Dab1 protein is thought to function downstream of the extracellular protein Reln during neuronal positioning. The structures of Dab proteins suggest that they mediate protein-protein or protein-membrane docking functions. Here we show that the amino-terminal phosphotyrosine-binding (PTB) domain of Dab1 binds to the transmembrane glycoproteins of the amyloid precursor protein (APP) and low-density lipoprotein receptor families and the cytoplasmic signaling protein Ship. Dab1 associates with the APP cytoplasmic domain in transfected cells and is coexpressed with APP in hippocampal neurons. Screening of a set of altered peptide sequences showed that the sequence GYXNPXY present in APP family members is an optimal binding sequence, with approximately 0.5 microM affinity. Unlike other PTB domains, the Dab1 PTB does not bind to tyrosine-phosphorylated peptide ligands. The PTB domain also binds specifically to phospholipid bilayers containing phosphatidylinositol 4P (PtdIns4P) or PtdIns4,5P2 in a manner that does not interfere with protein binding. We propose that the PTB domain permits Dab1 to bind specifically to transmembrane proteins containing an NPXY internalization signal.
B W Howell; L M Lanier; R Frank; F B Gertler; J A Cooper
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Molecular and cellular biology     Volume:  19     ISSN:  0270-7306     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  1999 Jul 
Date Detail:
Created Date:  1999-07-22     Completed Date:  1999-07-22     Revised Date:  2013-06-11    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  5179-88     Citation Subset:  IM    
Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
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MeSH Terms
Amino Acid Sequence
Amyloid beta-Protein Precursor / chemistry,  metabolism*
Binding Sites
Cloning, Molecular
Cytoplasm / metabolism
Glycoproteins / metabolism*
HeLa Cells
Membrane Glycoproteins / metabolism*
Membrane Lipids / metabolism*
Molecular Sequence Data
Nerve Tissue Proteins / genetics,  metabolism*
Peptides / metabolism
Phosphatidylinositols / metabolism
Phospholipids / metabolism*
Phosphoric Monoester Hydrolases / metabolism
Phosphotyrosine / metabolism
Receptors, LDL / metabolism
Recombinant Fusion Proteins / genetics,  metabolism
Saccharomyces cerevisiae
Subcellular Fractions
Tumor Cells, Cultured
Grant Support
Reg. No./Substance:
0/Amyloid beta-Protein Precursor; 0/Dab1 protein, mouse; 0/Glycoproteins; 0/Ligands; 0/Membrane Glycoproteins; 0/Membrane Lipids; 0/Nerve Tissue Proteins; 0/Peptides; 0/Phosphatidylinositols; 0/Phospholipids; 0/Receptors, LDL; 0/Recombinant Fusion Proteins; 21820-51-9/Phosphotyrosine; EC 3.1.3.-/INPPL1 protein, human; EC 3.1.3.-/Phosphoric Monoester Hydrolases

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