The Mammalian Numb Phosphotyrosine-binding Domain

Dho, Sascha E.; Jacob, Sara; Wolting, Cheryl; French, Michelle; Rohrschneider, Larry R.; McGlade, C. Jane

doi:10.1074/jbc.273.15.9179

Cited by 110 publications

(76 citation statements)

References 59 publications

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“…The PTB domain of CAPON is most similar to the PTB domain of mouse numb, which, like CAPON, lacks certain residues that are expected to contact the phosphotyrosine based on extrapolation from the crystal structure of the Shc PTB domain (36). In the case of numb, its protein targets lack phosphotyrosine, as exemplified by Numb-associated protein kinase (37) and LNX (38). Similarly, Dexras1, the other identified ligand of CAPON PTB domain, also has no requirement for phosphotyrosine for binding to occur (8).…”

Section: Discussionmentioning

confidence: 99%

Neuronal nitric-oxide synthase localization mediated by a ternary complex with synapsin and CAPON

Jaffrey

Benfenati

Snowman

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

105

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The specificity of the reactions of nitric oxide (NO) with its neuronal targets is determined in part by the precise localizations of neuronal NO synthase (nNOS) within the cell. The targeting of nNOS is mediated by adapter proteins that interact with its PDZ domain. Here, we show that the nNOS adapter protein, CAPON, interacts with synapsins I, II, and III through an N-terminal phosphotyrosinebinding domain interaction, which leads to a ternary complex comprising nNOS, CAPON, and synapsin I. The significance of this ternary complex is demonstrated by changes in subcellular localization of nNOS in mice harboring genomic deletions of both synapsin I and synapsin II. These results suggest a mechanism for specific actions of NO at presynaptic sites.

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Section: Discussionmentioning

confidence: 99%

Neuronal nitric-oxide synthase localization mediated by a ternary complex with synapsin and CAPON

Jaffrey

Benfenati

Snowman

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

105

View full text Add to dashboard Cite

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“…Additionally, the PTB domain of Shc has been shown to interact with PTP-PEST through an NPLH motif (Charest et al, 1996) and the PTB domains of X11 and FE65 (Borg et al, 1996) have been shown to interact with non-phosphorylated NPXY motifs. Similarly, the PTB domain of Numb has been shown to interact with non-phosphorylated (Dho et al, 1998) and non-NPXY motif-containing Chien et al, 1998) targets. This suggests that the speci®city of PTB domain binding may be more dependent upon tertiary structure rather than on a linear sequence.…”

Section: Discussionmentioning

confidence: 99%

The Tek/Tie2 receptor signals through a novel Dok-related docking protein, Dok-R

1998

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Tek/Tie2 is an endothelial cell-speci®c receptor tyrosine kinase that has been shown to play a role in vascular development of the mouse. Targeted mutagenesis of both Tek and its agonistic ligand, Angiopoietin-1, result in embryonic lethality, demonstrating that the signal transduction pathway(s) mediated by this receptor are crucial for normal embryonic development. In an attempt to identify downstream signaling partners of the Tek receptor, we have used the yeast two-hybrid system to identify phosphotyrosine-dependent interactions. Using this approach, we have identi®ed a novel docking molecule called Dok-R, which has sequence and structural homology to p62 dok and IRS-3. Mapping of the phosphotyrosine-interaction domain within Dok-R shows that Dok-R interacts with Tek through a PTB domain. Dok-R is coexpressed with Tek in a number of endothelial cell lines. We show that coexpression of Dok-R with activated Tek results in tyrosine phosphorylation of Dok-R and that rasGAP and Nck coimmunoprecipitate with phosphorylated Dok-R. Furthermore, Dok-R is constitutively bound to Crk presumably through the proline rich tail of Dok-R. The cloning of Dok-R represents the ®rst downstream substrate of the activated Tek receptor, and suggests that Tek can signal through a multitude of pathways.

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“…CAR may also interact with a component of the adherens junction, ␤-catenin, as has been reported in A549 cells (6). In addition, yeast-two-hybrid studies have shown that CAR interacts with Ligand of Numb-X (LNX) (7), a PDZ protein believed to regulate Notch signaling in the central nervous system; however, LNX is not known to associate with TJs (8,9).…”

mentioning

confidence: 91%

The Coxsackievirus and Adenovirus Receptor Interacts with the Multi-PDZ Domain Protein-1 (MUPP-1) within the Tight Junction

Coyne

Voelker

Pichla

et al. 2004

Journal of Biological Chemistry

113

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The coxsackievirus and adenovirus receptor (CAR) is a component of the epithelial cell tight junction. In a yeast two-hybrid screen we identified the multi-PDZ domain protein MUPP1 as an interaction partner for the CAR cytoplasmic domain. CAR and MUPP1 were found to colocalize at the tight junction, to coprecipitate from epithelial cells, and to interact in vitro. The interaction was found to specifically involve the PDZ-binding motif within the CAR C terminus and MUPP1 PDZ domain 13. In transfected cells, CAR recruited MUPP1 to cell-cell contacts. The inhibition of CAR expression with small interfering RNA inhibited MUPP1 localization to the tight junction. The results indicated that CAR interacts with MUPP1 and is involved in MUPP1 recruitment to the tight junction.

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The Mammalian Numb Phosphotyrosine-binding Domain

Cited by 110 publications

References 59 publications

Neuronal nitric-oxide synthase localization mediated by a ternary complex with synapsin and CAPON

Neuronal nitric-oxide synthase localization mediated by a ternary complex with synapsin and CAPON

The Tek/Tie2 receptor signals through a novel Dok-related docking protein, Dok-R

The Coxsackievirus and Adenovirus Receptor Interacts with the Multi-PDZ Domain Protein-1 (MUPP-1) within the Tight Junction

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