{"doi":"10.1172/jci132414","title":"Serine-threonine kinase ROCK2 regulates germinal center B cell positioning and cholesterol biosynthesis","abstract":"Germinal center (GC) responses require B cells to respond to a dynamic set of intercellular and microenvironmental signals that instruct B cell positioning, differentiation, and metabolic reprogramming. RHO-associated coiled-coil-containing protein kinase 2 (ROCK2), a serine-threonine kinase that can be therapeutically targeted by ROCK inhibitors or statins, is a key downstream effector of RHOA GTPases. Although RHOA-mediated pathways are emerging as critical regulators of GC responses, the role of ROCK2 in B cells is unknown. Here, we found that ROCK2 was activated in response to key T cell signals like CD40 and IL-21 and that it regulated GC formation and maintenance. RNA-Seq analyses revealed that ROCK2 controlled a unique transcriptional program in GC B cells that promoted optimal GC polarization and cholesterol biosynthesis. ROCK2 regulated this program by restraining AKT activation and subsequently enhancing FOXO1 activity. ATAC-Seq (assay for transposase-accessible chromatin with high-throughput sequencing) and biochemical analyses revealed that the effects of ROCK2 on cholesterol biosynthesis were instead mediated via a novel mechanism. ROCK2 directly phosphorylated interferon regulatory factor 8 (IRF8), a crucial mediator of GC responses, and promoted its interaction with sterol regulatory element-binding transcription factor 2 (SREBP2) at key regulatory regions controlling the expression of cholesterol biosynthetic enzymes, resulting in optimal recruitment of SREBP2 at these sites. These findings thus uncover ROCK2 as a multifaceted and therapeutically targetable regulator of GC responses.","journal":"Journal of Clinical Investigation","year":2020,"id":95806,"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":35,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9516,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":334718,"name":"Yurii Chinenov","orcid":"0000-0001-5226-8541","position":1,"is_corresponding":false},{"id":383407,"name":"Tania Pannellini","orcid":"0000-0002-0224-9921","position":2,"is_corresponding":false},{"id":476283,"name":"Danny Flores-Castro","orcid":null,"position":3,"is_corresponding":false},{"id":420516,"name":"Chao Ye","orcid":"0000-0002-9897-0085","position":4,"is_corresponding":false},{"id":420515,"name":"Sanjay Gupta","orcid":"0000-0003-1714-3895","position":5,"is_corresponding":false},{"id":420517,"name":"Michela Manni","orcid":"0000-0002-8916-1788","position":6,"is_corresponding":false},{"id":475455,"name":"James K. Liao","orcid":"0000-0001-9679-4252","position":7,"is_corresponding":false},{"id":420518,"name":"Alessandra B. Pernis","orcid":"0000-0001-8259-1446","position":8,"is_corresponding":false},{"id":420513,"name":"Edd Ricker","orcid":"0000-0001-8779-1105","position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":null,"created_at":"2026-07-18T22:33:57.534608Z","pmid":"32229726","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":[]}