{"doi":"10.1074/jbc.273.15.8867","title":"Coordinated Regulation of the Tyrosine Phosphorylation of Cbl by Fyn and Syk Tyrosine Kinases","abstract":null,"journal":"Journal of Biological Chemistry","year":1998,"id":680310,"datarank":0.7143260902196635,"base_score":4.762173934797756,"endowment":4.762173934797756,"self_citation_contribution":0.7143260902196635,"citation_network_contribution":0.0,"self_endowment_contribution":0.7143260902196635,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":116,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":391800,"name":"Chris Elly","orcid":null,"position":1,"is_corresponding":false},{"id":519562,"name":"Amnon Altman","orcid":"0000-0003-0717-5367","position":2,"is_corresponding":false},{"id":1777508,"name":"Yun-Cai Liu","orcid":null,"position":3,"is_corresponding":false},{"id":1412616,"name":"Marcel Deckert","orcid":"0000-0003-2094-559X","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Coordinated Regulation of the Tyrosine Phosphorylation of Cbl by Fyn and Syk Tyrosine Kinases","abstract":"Cross-linking of the T cell antigen receptor (TCR)-CD3 complex induces rapid tyrosine phosphorylation and activation of Src (Lck and Fyn) and Syk (Syk and Zap-70) family protein tyrosine kinases (PTKs) which, in turn, phosphorylate multiple intracellular substrates. Cbl is a prominent PTK substrate suggesting a pivotal role for it in early signal transduction events. However, the regulation of Cbl function and tyrosine phosphorylation in T cells by upstream PTKs remains poorly understood. In the present study, we used genetic and biochemical approaches to demonstrate that Cbl directly interacts with Syk and Fyn via its N-terminal and C-terminal regions, respectively. Tyr-316 of Syk was required for the interaction with Cbl as well as for the maximal tyrosine phosphorylation of Cbl. However, both wild-type Syk and Y316F-mutated Syk phosphorylated equally well the C-terminal fragment of Cbl in vivo, suggesting the existence of an alternative, N terminus-independent mechanism for the Syk-induced tyrosine phosphorylation of Cbl. This mechanism appears to involve Fyn, since, in addition to its association with the C-terminal region of Cbl, Fyn also associated with Syk and enhanced the Syk-induced tyrosine phosphorylation of Cbl. These findings implicate Fyn as an adaptor protein that facilitates the interaction between Syk and Cbl, and suggest that Src and Syk family PTKs coordinately regulate the tyrosine phosphorylation of Cbl.","is_dataset_classified":null,"base_score":4.762173934797756,"endowment":4.762173934797756,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"9535867","pmcid":null,"openalex_id":"https://openalex.org/W2090863009","authors":[],"funders":[{"funder_name":"NCI NIH HHS","grant_id":"CA35299","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"GM50819","title":null}],"total_grants":2,"fwci":4.8911,"citation_percentile":0.96034651,"influential_citations":0,"citation_trend":[{"year":2012,"count":8},{"year":2013,"count":2},{"year":2014,"count":1},{"year":2015,"count":3},{"year":2016,"count":1},{"year":2017,"count":1},{"year":2019,"count":1},{"year":2021,"count":2},{"year":2022,"count":1},{"year":2024,"count":1}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"http://www.jbc.org/article/S0021925818495762/pdf","host_type":"journal"},{"url":"http://www.jbc.org/article/S0021925818495762/pdf","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0021925818495762?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0021925818495762?httpAccept=text/plain","host_type":"publisher"},{"url":"https://syndication.highwire.org/content/doi/10.1074/jbc.273.15.8867","host_type":"publisher"},{"url":"https://doi.org/10.1074/jbc.273.15.8867","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/9535867","host_type":"repository"},{"url":"http://www.jbc.org/content/273/15/8867.full.pdf","host_type":"Unpaywall"}],"fields_of_study":["Protein Kinase Regulation and GTPase Signaling","Protein Tyrosine Phosphatases","14-3-3 protein interactions"],"mesh_terms":["Syk Kinase","Cloning, Molecular","Enzyme Precursors","Homeostasis","Humans","Phosphorylation","Protein-Tyrosine Kinases","Proto-Oncogene Proteins","Recombinant Fusion Proteins","Recombinant Proteins","Saccharomyces cerevisiae","Substrate Specificity","Transfection","Tyrosine","Retroviridae Proteins, Oncogenic","Phosphotyrosine","Jurkat Cells","Intracellular Signaling Peptides and Proteins","Oncogene Protein v-cbl","Proto-Oncogene Proteins c-fyn"],"keywords":["Syk","FYN","Phosphorylation","Tyrosine phosphorylation","Tyrosine kinase","Tyrosine","Cell biology","Proto-oncogene tyrosine-protein kinase Src","Kinase","Tyrosine-protein kinase CSK","SH2 domain","Chemistry","Protein-Tyrosine Kinases","Protein tyrosine phosphatase","Biology","Biochemistry","Signal transduction"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-17T14:50:40.177458Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}