{"doi":"10.33697/ajur.2022.068","title":"Novel Interactors of the SH2 Domain of the Signaling Adaptors CRK and CRKL Identified in Neuro2A Cells","abstract":"CT10 regulator of kinase (CRK) and CRK-like (CRKL) form a family of signaling adaptor proteins that serve important roles in the regulation of fundamental cellular processes, including cell motility and proliferation, in a variety of cell types. The Src Homology 2 (SH2) domain of CRK and CRKL interacts with proteins containing phosphorylated tyrosine-X-X-proline (pYXXP) motifs, facilitating complex formation during signaling events. A handful of CRK/CRKL-SH2-specific interactors have been identified to date, although in silico analyses suggest that many additional interactors remain to be found. To identify CRK/CRKL-SH2 interactors with potential involvement in neuronal development, we conducted a mass spectrometry-based proteomics screen using a neuronal cell line (Neuro2A, or N2A). This resulted in the identification of 132 (6 known and 126 novel) YXXP-containing CRK/CRKL-SH2 interactors, of which 77 were stimulated to bind to the CRK/CRKL-SH2 domain following tyrosine phosphatase inhibition. Approximately half of the proteins identified were common interactors of both the CRK- and CRKL-SH2 domains. However, both CRK family member SH2 domains exhibited unique binding partners across experimental replicates. These findings reveal an abundance of novel neuronal CRK/CRKL-SH2 domain binding partners and suggest that CRK family SH2 domains possess undescribed docking preferences beyond the canonical pYXXP motif. KEYWORDS: CRK; CRKL; SH2; LC-MS/MS; Proteomics; Neurodevelopment; Signal Transduction","journal":"American Journal of Undergraduate Research","year":2022,"id":288445,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9567,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":364787,"name":"Anna M. Schmoker","orcid":"0000-0003-2830-5650","position":1,"is_corresponding":false},{"id":862148,"name":"Shannon M. Bennett","orcid":"0000-0002-5008-6637","position":2,"is_corresponding":false},{"id":969657,"name":"Amara Chittenden","orcid":null,"position":3,"is_corresponding":false},{"id":969658,"name":"Chelsea B Darwin","orcid":null,"position":4,"is_corresponding":false},{"id":969659,"name":"Helena Gaffney","orcid":null,"position":5,"is_corresponding":false},{"id":654736,"name":"Hannah Lewis","orcid":"0000-0001-6584-6806","position":6,"is_corresponding":false},{"id":375027,"name":"Eliana Moskovitz","orcid":null,"position":7,"is_corresponding":false},{"id":969660,"name":"Jonah Rehak","orcid":null,"position":8,"is_corresponding":false},{"id":969661,"name":"Anna Renzi","orcid":null,"position":9,"is_corresponding":false},{"id":969662,"name":"Claire Rothfelder","orcid":null,"position":10,"is_corresponding":false},{"id":969663,"name":"Adam Slamin","orcid":null,"position":11,"is_corresponding":false},{"id":969664,"name":"Megan Tammaro","orcid":null,"position":12,"is_corresponding":false},{"id":969665,"name":"Leigh Sweet","orcid":null,"position":13,"is_corresponding":false},{"id":364789,"name":"Bryan A. Ballif","orcid":"0000-0001-7650-3817","position":14,"is_corresponding":false},{"id":969249,"name":"Caroline Dumas","orcid":"0000-0003-0069-4463","position":0,"is_corresponding":true}],"reference_count":17,"raw_metadata":null,"created_at":"2026-07-19T00:30:14.968626Z","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":[]}