The disabled 1 phosphotyrosine-binding domain binds to the internalization signals of transmembrane glycoproteins and to phospholipids.

2.50
Hdl Handle:
http://hdl.handle.net/10033/620751
Title:
The disabled 1 phosphotyrosine-binding domain binds to the internalization signals of transmembrane glycoproteins and to phospholipids.
Authors:
Howell, B W; Lanier, L M; Frank, R; Gertler, F B; Cooper, J A
Abstract:
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.
Affiliation:
Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
Citation:
The disabled 1 phosphotyrosine-binding domain binds to the internalization signals of transmembrane glycoproteins and to phospholipids. 1999, 19 (7):5179-88 Mol. Cell. Biol.
Journal:
Molecular and cellular biology
Issue Date:
Jul-1999
URI:
http://hdl.handle.net/10033/620751
PubMed ID:
10373567
Type:
Article
Language:
en
ISSN:
0270-7306
Appears in Collections:
Publications of the research group Chemical Biology (CBIO)

Full metadata record

DC FieldValue Language
dc.contributor.authorHowell, B Wen
dc.contributor.authorLanier, L Men
dc.contributor.authorFrank, Ren
dc.contributor.authorGertler, F Ben
dc.contributor.authorCooper, J Aen
dc.date.accessioned2017-01-26T14:47:16Z-
dc.date.available2017-01-26T14:47:16Z-
dc.date.issued1999-07-
dc.identifier.citationThe disabled 1 phosphotyrosine-binding domain binds to the internalization signals of transmembrane glycoproteins and to phospholipids. 1999, 19 (7):5179-88 Mol. Cell. Biol.en
dc.identifier.issn0270-7306-
dc.identifier.pmid10373567-
dc.identifier.urihttp://hdl.handle.net/10033/620751-
dc.description.abstractDisabled 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.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject.meshAmino Acid Sequenceen
dc.subject.meshAmyloid beta-Protein Precursoren
dc.subject.meshAnimalsen
dc.subject.meshBinding Sitesen
dc.subject.meshCloning, Molecularen
dc.subject.meshCytoplasmen
dc.subject.meshGlycoproteinsen
dc.subject.meshHeLa Cellsen
dc.subject.meshHumansen
dc.subject.meshLigandsen
dc.subject.meshMembrane Glycoproteinsen
dc.subject.meshMembrane Lipidsen
dc.subject.meshMiceen
dc.subject.meshMolecular Sequence Dataen
dc.subject.meshNerve Tissue Proteinsen
dc.subject.meshPeptidesen
dc.subject.meshPhosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatasesen
dc.subject.meshPhosphatidylinositolsen
dc.subject.meshPhospholipidsen
dc.subject.meshPhosphoric Monoester Hydrolasesen
dc.subject.meshPhosphorylationen
dc.subject.meshPhosphotyrosineen
dc.subject.meshReceptors, LDLen
dc.subject.meshRecombinant Fusion Proteinsen
dc.subject.meshSaccharomyces cerevisiaeen
dc.subject.meshSubcellular Fractionsen
dc.subject.meshTumor Cells, Cultureden
dc.titleThe disabled 1 phosphotyrosine-binding domain binds to the internalization signals of transmembrane glycoproteins and to phospholipids.en
dc.typeArticleen
dc.contributor.departmentFred Hutchinson Cancer Research Center, Seattle, Washington 98109, USAen
dc.identifier.journalMolecular and cellular biologyen

Related articles on PubMed

This item is licensed under a Creative Commons License
Creative Commons
All Items in HZI are protected by copyright, with all rights reserved, unless otherwise indicated.