Browse
Submit Data
Databases
API
Help

Dataset Information

346 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Comprehensive Identification of Phosphorylation Sites on the Numb Endocytic Adaptor Protein

ABSTRACT: Numb is an endocytic adaptor protein that functions in the endocytosis and intracellular trafficking of membrane receptors and adhesion molecules. Numb localization and function have been shown to be regulated by phosphorylation through atypcial protein kinase C at several key sites. Here, we use Liquid Chromatogrpahy, Tandem Mass Spectrometry to identify additional Numb phosphorylation sites not yet characterized.

INSTRUMENT(S): LTQ Orbitrap, LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

DISEASE(S): Brain Cancer

SUBMITTER: Jonathan Krieger

LAB HEAD: Jane McGlade

PROVIDER: PXD000997 | Pride | 2014-12-16

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Publications

Comprehensive identification of phosphorylation sites on the Numb endocytic adaptor protein.

Krieger Jonathan R JR Taylor Paul P Moran Michael F MF McGlade C Jane CJ

Proteomics 20150101 2-3

Numb is an adaptor protein that functions in the endocytosis and intracellular trafficking of membrane receptors and adhesion molecules. Previous studies have indicated that Numb localization and function are regulated through phosphorylation by atypical protein kinase C at several key sites. Here, using LC-MS/MS, we report the identification of 25 serine/threonine Numb phosphorylation sites, and a single tyrosine phosphorylation site. Amino acid sequences flanking several of the sites identifie ...[more]

PMID: 25403733

Similar Datasets

Comprehensive Identification of Phosphorylation Sites on the Numb Endocytic Adaptor Protein

Project description:Numb is an endocytic adaptor protein that functions in the endocytosis and intracellular trafficking of membrane receptors and adhesion molecules. Numb localization and function have been shown to be regulated by phosphorylation through atypcial protein kinase C at several key sites. Here, we use Liquid Chromatogrpahy, Tandem Mass Spectrometry to identify additional Numb phosphorylation sites not yet characterized.

2016-10-04 | MSV000080218 | MassIVE

Endocytic Adaptor Protein Tollip Inhibits Canonical Wnt Signaling.

Project description: Not available

| S-EPMC4482507 | biostudies-literature

A selective autophagy pathway for endocytic protein condensates

Project description:Autophagy eliminates cytoplasmic content selected by autophagy receptors, which link cargoes to the membrane bound autophagosomal ubiquitin-like protein Atg8/LC3. Here, we discover a selective autophagy pathway for protein condensates formed by endocytic proteins. In this pathway, the endocytic yeast protein Ede1 functions as a selective autophagy receptor. Distinct domains within Ede1 bind Atg8 and mediate phase separation into condensates. Both properties are necessary for an Ede1-dependent autophagy pathway for endocytic proteins, which differs from regular endocytosis, does not involve other known selective autophagy receptors, but requires the core autophagy machinery. Cryo-electron tomography of Ede1-containing condensates – at the plasma membrane and in autophagic bodies – shows a phase-separated compartment at the beginning and end of the Ede1-mediated selective autophagy pathway. Our results imply an important role of autophagy in surveillance of membraneless compartments

2020-11-23 | PXD019083 | Pride

Morphogen Stimulated Endocytic Recycling Drives Cytoneme Loading for Mammalian Tissue Patterning

Project description:During development, morphogens build tissues by instructing cell fate across long distances. Directly visualizing morphogen transport in situ has been unfeasible, so the molecular mechanisms ensuring successful morphogen delivery remain unclear. To tackle this longstanding problem, we developed a mouse model for compromised Sonic Hedgehog (SHH) morphogen delivery and discovered that endocytic recycling promotes SHH loading into signaling filopodia called cytonemes. We optimized methods to preserve in vivo cytonemes for advanced microscopy and show endogenously-expressed SHH localized to cytonemes in developing mouse neural tubes. Depletion of SHH from neural tube cytonemes alters neuronal cell fates and compromises neurodevelopment. Mutation of the filopodial motor Myosin 10 (MYO10) reduces cytoneme length and density, which corrupts neuronal signaling activity of both SHH and WNT. Combined, these results demonstrate that cytoneme-based signal transport provides essential contributions to morphogen dispersion during mammalian tissue development and suggest MYO10 is a key regulator of cytoneme function.

2024-01-02 | GSE242161 | GEO

Negative regulation of the endocytic adaptor disabled-2 (Dab2) in mitosis.

Project description: Not available

| S-EPMC3037652 | biostudies-literature

p97/VCP promotes the recycling of endocytic cargo

Project description:The endocytic pathway is of central importance for eukaryotic cells, as it enables uptake of extracellular materials, membrane protein quality control and recycling, as well as modulation of receptor signaling. While the ATPase p97 (VCP, Cdc48) has been found to be involved in the fusion of early endosomes and endolysosomal degradation, its role in endocytic trafficking is still incompletely characterized. Here, we identify myoferlin (MYOF), a ferlin family member with functions in membrane trafficking and repair, as a hitherto unknown p97 interactor. The interaction of MYOF with p97 depends on the cofactor PLAA previously linked to endosomal sorting. Besides PLAA, shared interactors of p97 and MYOF comprise several proteins involved in endosomal recycling pathways, including Rab11, Rab14 and the transferrin receptor CD71. Accordingly, a fraction of p97 and PLAA localizes to MYOF-, Rab11-, and Rab14-positive endosomal compartments. Pharmacological inhibition of p97 delays transferrin recycling, indicating that p97 promotes not only the lysosomal degradation, but also the recycling of endocytic cargo.

2023-09-28 | PXD041169 | Pride

Swiprosin1 controls cargo-specific entry to clathrin and dynamin-independent endocytic pathway

Project description:The clathrin and dynamin-independent endocytic pathway (CLIC-GEEC) is the major route of internalization of a large fraction of glycosylphosphatidylinositol-anchored proteins (GPI-APs) and other cell surface receptors. Unlike the clathrin-dependent endocytic pathway, where adaptors recruited to the endocytic pit provide the clues to recruit specific cargo, the CLIC-GEEC pathway is considered to take up portions of the membrane without any specificity. Here, we identified actin-binding protein swiprosin1 as the first cargo adaptor for the CLIC-GEEC pathway. We found that swiprosin1 interacts with active Rab21, a known regulator of integrin endocytosis, and couples Rab21 and the integrin cargo to the CLIC-GEEC endocytic machinery. Our work also identified the previously unknown pathway by which Rab21 mediates integrin endocytosis and linked the CLIC-GEEC pathway to integrin-dependent cancer cell invasion.

2021-08-18 | PXD016478 | Pride

The endocytic TPLATE complex internalizes ubiquitinated plasma membrane cargo

Project description:Endocytosis controls the perception of stimuli by modulating protein abundance at the plasma membrane. In plants, clathrin-mediated endocytosis is the most prominent internalization pathway and relies on two multimeric adaptor complexes, the AP-2 and the TPLATE complex (TPC). Ubiquitination is a well-established modification triggering endocytosis of cargo proteins, but how this modification is recognized to initiate the endocytic event remains elusive. Here, we show that TASH3, one of the large subunits of TPC, recognizes ubiquitinated cargo at the plasma membrane via its SH3 domain-containing appendage. TASH3 lacking this evolutionary specific appendage modification allows TPC formation, but the plants show severely reduced endocytic densities, which correlates with reduced endocytic flux. Moreover, comparative plasma membrane proteomics identified differential accumulation of multiple ubiquitinated cargo proteins for which we confirm altered trafficking. Our findings position TPC as a key player for ubiquitinated cargo internalization, allowing future identification of target proteins under specific stress conditions.

2023-03-11 | PXD035444 | Pride

The endocytic adaptor proteins of pathogenic fungi: charting new and familiar pathways.

Project description: Not available

| S-EPMC3516230 | biostudies-literature

CRACR2a is a calcium-activated dynein adaptor protein that regulates endocytic traffic.

Project description: Not available

| S-EPMC6504896 | biostudies-literature