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available"],"repository":["GPMDB"],"pubmed_abstract":["Aberrant expression, activation, and stabilization of epidermal growth factor receptor (EGFR) are causally associated with several human cancers. Post-translational modifications and protein-protein interactions directly modulate the signaling and trafficking of the EGFR. Activated EGFR is internalized by endocytosis and then either recycled back to the cell surface or degraded in the lysosome. EGFR internalization and recycling also occur in response to stresses that activate p38 MAP kinase. Mass spectrometry was applied to comprehensively analyze the phosphorylation, ubiquitination, and protein-protein interactions of wild type and endocytosis-defective EGFR variants before and after internalization in response to EGF ligand and stress. Prior to internalization, EGF-stimulated EGFR accumulated ubiquitin at 7 K residues and phosphorylation at 7 Y sites and at S(1104). Following internalization, these modifications diminished and there was an accumulation of S/T phosphorylations. EGFR internalization and many but not all of the EGF-induced S/T phosphorylations were also stimulated by anisomycin-induced cell stress, which was not associated with receptor ubiquitination or elevated Y phosphorylation. EGFR protein interactions were dramatically modulated by ligand, internalization, and stress. In response to EGF, different E3 ubiquitin ligases became maximally associated with EGFR before (CBL, HUWE1, and UBR4) or after (ITCH) internalization, whereas CBLB was distinctively most highly EGFR associated following anisomycin treatment. Adaptin subunits of AP-1 and AP-2 clathrin adaptor complexes also became EGFR associated in response to EGF and anisomycin stress. Mutations preventing EGFR phosphorylation at Y(998) or in the S(1039) region abolished or greatly reduced EGFR interactions with AP-2 and AP-1, and impaired receptor trafficking. These results provide new insight into spatial, temporal, and mechanistic aspects of EGFR regulation."],"pubmed_title":["Proteomic analysis of the epidermal growth factor receptor (EGFR) interactome and post-translational modifications associated with receptor endocytosis in response to EGF and stress."],"pubmed_authors":["Tong Jiefei J,Taylor Paul P,Moran Michael F MF,","Tong Jiefei J, Taylor Paul P, Moran Michael F MF"],"name_synonyms":["receptor tyrosine-protein kinase erbB-1, reactivity, EGF receptor binding, transforming growth factor alpha receptor ligand, epidermal growth factor., proto-oncogene c-ErbB-1, Wa5, plasma membrane invagination, epidermal growth factor receptor ligand, URG, TGF-alpha receptor activity, ERBB, EGFR, EGFR binding, Epidermal growth factor, TGF-alpha receptor binding, Errb1, ERBB1, Endocytoses, wa-2, nonselective vesicle endocytosis, mENA, PIG61, endocytic import into cell, vesicle endocytosis, transforming growth factor alpha receptor binding, EGF, transforming growth factor alpha, epidermal growth factor receptor activity, HOMG4, wa2, Errp, AI790464, Erbb, AI552599, responsivity, proteomic analysis, EGF receptor ligand, 9030024J15Rik, EGF receptor activity, transforming growth factor-alpha receptor activity, response, associated, TGFalpha receptor binding, Urogastrone, HER1, NISBD2"],"description_synonyms":["ass, domestic ass, receptor tyrosine-protein kinase erbB-1, atypia, data, EGF receptor binding, CTLN1, proto-oncogene c-ErbB-1, plasma membrane invagination, aberrant, functional failure, Wa5, mol, Ass-1, TGF-alpha receptor activity, ERBB, Phosphorylations, A4, TGF-alpha receptor binding, Errb1, Endocytoses, defective, nonselective vesicle endocytosis, disfunctional, mENA, Cell, phosphorylation, TYPE, LGMD2C, PIG61, Spectroscopy, DAGA4, polypeptide, African ass, endocytic import into cell, vesicle endocytosis, transforming growth factor alpha, epidermal growth factor receptor activity, wa2, AI790464, AA408052, AI552599, responsivity, fold, EGF receptor activity, atypical, Analysis, failure, MAM, SCG3, Urogastrone, epidermal growth factor, reactivity, transforming growth factor alpha receptor ligand, Ubiquitylation, donkey, DMDA1, epidermal growth factor receptor ligand, URG, cell, EGFR, Spectrum, African wild ass, Spectrometry, EGFR binding, Epidermal growth factor, proteins, ERBB1, Somali wild ass, wa-2, ASS, transforming growth factor alpha receptor binding, EGF, DMDA, ligand., HOMG4, Errp, Erbb, SCARMD2, EGF receptor ligand, 9030024J15Rik, ubiquitination, transforming growth factor-alpha receptor activity, response, TGFalpha receptor binding, HER1, NISBD2"],"pubmed_title_synonyms":["receptor tyrosine-protein kinase erbB-1, reactivity, EGF receptor binding, transforming growth factor alpha receptor ligand, epidermal growth factor., proto-oncogene c-ErbB-1, Wa5, plasma membrane invagination, epidermal growth factor receptor ligand, URG, TGF-alpha receptor activity, ERBB, EGFR, EGFR binding, Epidermal growth factor, TGF-alpha receptor binding, Errb1, ERBB1, Endocytoses, wa-2, nonselective vesicle endocytosis, mENA, PIG61, endocytic import into cell, vesicle endocytosis, transforming growth factor alpha receptor binding, EGF, transforming growth factor alpha, epidermal growth factor receptor activity, HOMG4, wa2, Errp, AI790464, Erbb, AI552599, responsivity, proteomic analysis, EGF receptor ligand, 9030024J15Rik, EGF receptor activity, transforming growth factor-alpha receptor activity, response, associated, TGFalpha receptor binding, Urogastrone, HER1, NISBD2"],"pubmed_abstract_synonyms":["AP-2, AP-1, clathrin adaptor, AIP4, A4, TGF-alpha receptor binding, Errb1, nonselective vesicle endocytosis, Homo sapiense, CBL2, phosphorylation, temporal, cell associated, PIG61, NSLL, Mutations, dysfunctional, endocytic import into cell, Homo sapien, AP2TF, AI552599, Homo sapians, responsivity, 3, Analysis, LASU1, present in fewer numbers in organism, Mass Spectrum Analysis, treatment, Junc, Homo sapients, Ubiquitylation, High Mobility Protein 20, Analyses, Flagecidin, Mitogen activated protein kinase 14, RBAF600, hypoplasia, Ubiquitin-related 1, proteins, elevated, ARF-BP1, APF-1, transforming growth factor alpha receptor binding, A930005E13Rik, decreased, Homo sapience, signaling process, disease management, c-Jun, 9030024J15Rik, ubiquitination, p600, associated, AP-2 transcription factor, Home sapiens, mKIAA0462, NISBD2, single organism signaling, accumulated, ATR, 8030492O04Rik, C-CBL, aberrant, Wa5, functional failure, 6.3.2.-, incomplete, 4732447J05Rik, C430014N20Rik, Gm1666, CEP52, Spectrum Analysis, results, partial functionality, Spectroscopy, 4beta))-, abolished, vesicle endocytosis, Ap-2 (a), wa2, Homo sapian, Ap2tf, failure, regulation., Urogastrone, Arf-bp1, activation, 5430439H10Rik, Ubiquitin, D930005K06Rik, AIF4, EGFR, Spectrometry, Human Ubiquitin, Itch, Epidermal growth factor, pooled, AP-2alpha, lacks function of type, Homo sapines, human, low functionality, DMDA, G0S3, c-Cbl, p38 MAP kinase, TFAP2, cell bound, TGFalpha receptor binding, Activating enhancer-binding protein 2-alpha, receptor tyrosine-protein kinase erbB-1, RNF55, atypia, RNF56, biological signaling, EGF receptor binding, MULE, human being, Lysosome, proto-oncogene c-ErbB-1, GOS3, p55, impaired, Synthetases, Endocytoses, ATP Dependent Proteolysis Factor 1, AI429560, GOSB, Spectrum Analyses, disfunctional, Ubiquitin carboxyl extension protein 80, FRA11B, mENA, TYPE, Human, dJ468O1.1, DAGA4, Homo spaiens, (2R-(2alpha, N28143, reduced, AI790464, subnumerary, 3-acetate, Mass, EGF receptor activity, HMG-20, atypical, tiny, ubiquitin-like protein modifier, MAM, Atrophin-1-interacting protein 4, SCG3, epidermal growth factor, 6720481N21Rik, Mass Spectroscopy, RGD1561386, 2-((4-methoxyphenyl)methyl)-, reactivity, 1810009A16Rik, transforming growth factor alpha receptor ligand, epidermal growth factor receptor ligand, URG, Ib772, cell, AU041296, ligand, dysfunction, EGFR binding, Tcfap2a, HECTH9, decreased number, man, C230047C07Rik, 40S ribosomal protein S27a, Mule, HSPC272, HOMG4, Homo sampiens, ubiquitin, EGF receptor ligand, cob, protein tagging activity, high elevation, URE-B1, ADMFD, incidence, small, AI851073, plasma membrane invagination, TGF-alpha receptor activity, Zubr1, ERBB, c-jun, Phosphorylations, defective, Mitogen-activated protein kinase 14, 3alpha, isoform CRA_b, Cell, LGMD2C, AP2alpha, polypeptide, UREB1, Activator protein 2, Ubiquitin A-52 residue ribosomal protein fusion product 1, transforming growth factor alpha, epidermal growth factor receptor activity, Ubiquitin-related 2, Synthetase, sequence, A130065M08, Ureb1, Homo sapeins, ATP-Dependent Proteolysis Factor 1, Mass Spectrum Analyses, Cbl-b, Mass Spectrum, covalent modifier, Ap2, BOFS, DMDA1, underdeveloped, Humo sapiens, ERBB1, wa-2, cblB, ZUBR1, primary structure of sequence macromolecule, signalling, CFAP23, AP1, having decreased function, Homo spiens, EGF, 4-Pyrrolidinediol, C-FOS, \"human\" EXACT genbank_common_name [], signalling process, 60S ribosomal protein L40, Errp, Erbb, cbl, Cbl-2, Gm1718, SCARMD2, C80292, NFE2-associated polypeptide 1, Ubiquitin-related, transforming growth factor-alpha receptor activity, response, NAPP1, Gm1032, HER1, AP2-alpha"],"view_count":["39"],"citation_count":["0"],"search_count":["5"],"full_dataset_link":["http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310004705"],"search_domains":["dbgap_ncbi~0","patentfamilies~0","rfam~0","merops~0","complex-portal~0","uniprot~0","wormbaseparasite~0","embl-covid19~0","reactome~0","emdb~0","wgs_masters~0","ebiweb_resources~0","opentargets_genetics~0","biomodels_all~0","ipd-mhc~0","ebiweb_teams~0","taxonomy~0","genome_assembly~0","sc-experiments~0","ebiweb_people~0","enzymeportal_enzymes~0","ipd-nhkir~0","cellosaurus~0","pdbe~0","chebi~0","patentproteins~0","interpro7~0","uniref~0","chembl~0","pdbekb~0","gpcrdb~0","hgnc~0","sc-genes~0","intact~0","rhea~0","ebiweb_training~0","alphafold~0","imgt-hla~0","patentnucleotides~0","ensemblroot~0","eva_studies~0","non-coding~0","europepmc~0","pubmed~1","identifiers_registry~0","pdbechem~0","hpa-covid19~0","eva-variants-covid19~0","biosamples~0","gwas_catalog~0","biotools~0","tls_masters~0","mesh~0","coding~0","sra~0","opentargets~0","efo~0","embl-pathogen~0","project~0","pride~1","human_diseases~0","geo_datasets~0","embl~0","treefam~0","uniparc~0","ols~0","dgva~0","intenz~0","go~0","tsa_masters~0","biosamples-covid19~0","ebiweb_corporate~0","omim~0","lrg~0","earlycause-molecular-sequences~0","ipd-kir~0","empiar~0","rnacentral~0","orcid_data_claims~0","gpmdb~2","lineage-covid19~0","metagenomics~0","pfam~0","pride archive~1","varsite~0"],"reanalysis_count":["0"],"submitter_keywords":["Resource Reanalysis"],"citation_count_scaled":["0.0"],"reanalysis_count_scaled":["0.0"],"view_count_scaled":["0.012029611351017891"],"download_count_scaled":["0.0"],"normalized_connections":["1.0"],"additional_accession":[]},"is_claimable":false,"name":"Proteomic analysis of the epidermal growth factor receptor (EGFR) interactome and post-translational modifications associated with receptor endocytosis in response to EGF and stress.","description":"Data from ProteomeXchange, PXD ID: PXD000788. File: T1041A_Cont3.mzml. Published as part of Mol Cell Proteomics. 2014 Jul;13(7):1644-58  . From the Abstract: {{i}} ass spectrometry was applied to comprehensively analyze the phosphorylation, ubiquitination, and protein-protein interactions of wild type and endocytosis-defective EGFR variants before and after internalization in response to EGF ligand and stress. {{/i}}","dates":{"submission":"2014-10-25"},"accession":"GPM32310004705","cross_references":{"pubmed":["24797263"],"Pride":["PXD000788"],"pride":[],"Pride Archive":["PXD000788"]}}