{"doi":"10.1210/endocr/bqaf003","title":"Identification of βIIΣ1-Spectrin as a Binding Partner of the GH-regulated Human Obesity Scaffold Protein SH2B1","abstract":"SH2B1β is a multifunctional scaffold protein that modulates cytoskeletal processes such as cellular motility and neurite outgrowth. To identify novel SH2B1β-interacting proteins involved in these processes, a yeast 2-hybrid assay was performed. The C-terminal 159 residues of the cytoskeleton structural protein, βIIΣ1-spectrin, interacted with the N-terminal 260 residues of SH2B1β, a region implicated in SH2B1β enhancement of cell motility and localization at the plasma membrane. The interaction between SH2B1β and βIIΣ1-spectrin (2205-2363) requires residues 1 through 150 in SH2B1β, with residues 105 through 120 playing a key role. While βIIΣ1-spectrin (2205-2363) was expressed throughout the cell, it colocalized with SH2B1β when coexpressed with SH2B1β mutants with varied intracellular localizations. The SH2B1β-βIIΣ1-spectrin (2205-2363) interaction impaired the ability of SH2B1β to enter the nucleus. A slightly larger βIIΣ1-spectrin fragment (2170-2363) with an intact pleckstrin homology domain localized primarily to the plasma membrane and cytoplasm, similar to SH2B1β. Similarly, full-length βIIΣ1-spectrin colocalized at the plasma membrane and cytoplasm with SH2B1β as well as the SH2B1β-regulated tyrosine kinase, JAK2. Phosphorylation of spectrins has been shown to regulate their localization and function. Coexpression of βIIΣ1-spectrin, JAK2, and SH2B1β resulted in SH2B1β-dependent tyrosyl phosphorylation of βIIΣ1-spectrin. Finally, stimulation with GH induced formation of an endogenous complex containing βII-spectrin, SH2B1, and JAK2 in 3T3-F442A cells and increased tyrosyl phosphorylation of βII-spectrin. Our results identify a novel interaction between SH2B1β, βIIΣ1-spectrin, and JAK2 resulting in JAK2- and SHB1-dependent tyrosyl phosphorylation of βII-spectrin. This raises the possibility that the many other ligand-activated tyrosine kinases that signal through SH2B1 form similar complexes with βIIΣ1-spectrin.","journal":"Endocrinology","year":2025,"id":560273,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9543,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1462553,"name":"Liliya Mancour","orcid":null,"position":1,"is_corresponding":false},{"id":946400,"name":"Lawrence S. Argetsinger","orcid":"0000-0001-6777-8309","position":2,"is_corresponding":false},{"id":1462554,"name":"Stephen Archer","orcid":null,"position":3,"is_corresponding":false},{"id":946401,"name":"Christin Carter-Su","orcid":"0000-0001-5266-1271","position":4,"is_corresponding":false},{"id":797340,"name":"Nathan Lanning","orcid":"0000-0002-0983-7451","position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":null,"created_at":"2026-07-19T02:55:42.883572Z","pmid":"39801013","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":[]}