{"title":"Mechanical constraints regulate embryonic stem cell mitosis in the developing brain.","authors":"Véronique Marthiens,Lin Jawish,Margaux Malosse,Clara Basto,Denis Krndija,Anne-Sophie Macé,Elmar Laigna,Antonia Terrizzano,Corentin Peyret,Teng Pan,Olivier Zajac,Louisiane Perrin,Elsa Logarinho,Catherine Villard,Renata Basto","doi":"10.1038/s44318-026-00848-3","DOIUrl":"https://doi.org/10.1038/s44318-026-00848-3","url":null,"abstract":"Research on mitosis has predominantly examined cell-autonomous mechanisms, yet its regulation and consequences within the broader physiological context remain largely unexplored. It remains, therefore, unknown whether and how spindle assembly and chromosome segregation are influenced by tissue properties. We have investigated this question in the mammalian embryonic brain, using high-resolution microscopy combined with pharmacological perturbations and minimal cell systems to break down the contribution of tissue environment to mitotic fidelity. We found that cell density imposes biomechanical constraints upon the apical radial glial (aRG) cell population during their highly proliferative period, which enhances spindle pole microtubule polymerization rates and potentiates chromosome mis-segregation. Mechanistically, we show that cortical tension relying on branched actin organization at the cell cortex conveys mechanical stress exerted by cell density. We identified the microtubule depolymerase MCAK/Kif2C as a critical effector downstream of cortical actin, linking actin dynamics to spindle pole activity. Altogether, our findings demonstrate that aRG are mechanosensitive during their expansion phase, and that excessive biomechanical stress, imposed by high cell density in developing tissues, can disrupt mitotic fidelity.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"39 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148416616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Oncogenic EGFR rewires STING-TBK1 signalosomes to license DNA damage tolerance in NSCLC.","authors":"Qin Shen,Chen Mei,Yidan Chen,Qian Zhang,Qingzhe Wu,Xinyuan Yu,Fei Zhang,Shengduo Liu,Chen Chen,Cunqi Ye,Qi Zhang,Xin-Hua Feng,Li Shen,Hai Song,Tingbo Liang,Penghong Song,Bing Xia,Pinglong Xu","doi":"10.1038/s44318-026-00856-3","DOIUrl":"https://doi.org/10.1038/s44318-026-00856-3","url":null,"abstract":"EGFR hotspot mutations (mEGFR), including primary L858R, exon 19 deletion, and secondary T790M, are pivotal oncogenic drivers in human non-small cell lung cancer (NSCLC). At the same time, NSCLC resistance to third-generation tyrosine kinase inhibitors (TKIs) is a major clinical challenge and remains mechanistically unresolved. Here, we uncover a previously unrecognized tumor cell-intrinsic mechanism in which mutant EGFR (mEGFR) exploits innate immune signaling via the cGAS-STING-TBK1 pathway to sustain oncogenic signaling and therapeutic resistance. Mechanistically, mutant EGFR kinase aberrantly associates with STING signalosomes and phosphorylates STING (Y245/Y314) and TBK1 (Y577/Y677), stabilizing and hyperactivating TBK1 and establishing an unexpected kinase loop critical for DNA damage repair. Genetic or pharmacological disruption of mEGFR-STING-TBK1 coupling sensitizes resistant patient-derived NSCLC organoids to chemotherapy. Combining TBK1 inhibition with cisplatin suppressed mEGFR-driven tumors in murine models of spontaneous and immunocompetent NSCLC and in patient-derived organoids. Our findings suggest a new function of cGAS-STING in DNA damage tolerance, its paradoxical exploitation by oncogenic driver mutations, and an innate immune therapeutic vulnerability in NSCLC.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148416617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The EMBO JournalPub Date : 2026-07-09DOI: 10.1038/s44318-026-00853-6
Grace I Carey,Maria Vega-Sendino,Desiree Tillo,Sarah C Hoelscher,Amir Khan,Ian Taukulis,Teresa Olbrich,Bechara Saykali,Andy D Tran,Bhavya Soni,Anna Lee Fong,Melissa Mikolaj,Adam Harned,Kedar Narayan,Michael J Kruhlak,Michael Kelly,Ning Qing Liu,Elzo de Wit,Sergio Ruiz
{"title":"Alterations in chromatin organization promote totipotent-like features in a DPPA2/DUX-dependent manner.","authors":"Grace I Carey,Maria Vega-Sendino,Desiree Tillo,Sarah C Hoelscher,Amir Khan,Ian Taukulis,Teresa Olbrich,Bechara Saykali,Andy D Tran,Bhavya Soni,Anna Lee Fong,Melissa Mikolaj,Adam Harned,Kedar Narayan,Michael J Kruhlak,Michael Kelly,Ning Qing Liu,Elzo de Wit,Sergio Ruiz","doi":"10.1038/s44318-026-00853-6","DOIUrl":"https://doi.org/10.1038/s44318-026-00853-6","url":null,"abstract":"2-cell like cells (2CLC) are a transiently cycling population of cells with totipotent-associated features. Although CTCF depletion induces 2CLC conversion in mouse ESC, whether this reprogramming is a consequence of disrupted higher-order chromatin organization or of CTCF-specific functions remained unclear. Here, we show that depletion of the cohesin release factor WAPL in ESC also promotes 2CLC reprogramming, which is increased by CTCF co-depletion. Single-cell RNA-seq/ATAC-seq analyses in CTCF/WAPL-depleted ESC revealed that chromatin accessibility precedes 2C-associated gene expression. Moreover, we identified ARID3A as a transcription factor that regulates the extent of 2CLC conversion following WAPL/CTCF depletion. Although WAPL or CTCF depletion induces distinct transcriptional changes in human ESC, these do not resemble transcriptional programs of early human embryogenesis, suggesting limited evolutionary conservation. Finally, we demonstrate that 2CLC conversion mediated by alterations in chromatin organization depends on the DPPA2/DUX axis and correlates with nucleolar integrity. Together, these findings establish a mechanistic link between higher-order chromatin organization and totipotency-like cell identity in mice.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148416618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Local autophagy impairment triggers brain-wide presynaptic remodeling and resilience.","authors":"David Toppe,Sheng Huang,Janine Lützkendorf,Pin-Lian Jiang,Raquel Suárez-Grimalt,Alexander Neumann,Zhiying Zhao,Péter Lőrincz,Lisa Scheunemann,Gábor Juhász,Fan Liu,Marta Maglione,Stephan J Sigrist","doi":"10.1038/s44318-026-00847-4","DOIUrl":"https://doi.org/10.1038/s44318-026-00847-4","url":null,"abstract":"Neural circuits must remain functionally stable while adapting to changing demands and levels of stress. While this balance is thought to rely on plasticity programs integrating molecular and activity-dependent signals, mechanistic models of how such adaptations are orchestrated remain limited. Here, we show that impairment of autophagy in the Drosophila mushroom body (MB) induces brain-wide, post-transcriptional remodeling of presynaptic active zones, characterized by increased expression levels of active zone scaffold proteins, reduced abundance of calcium channel subunits, and elevated levels of Shaker-type potassium channels. This remodeling promotes organismal resilience, as reflected by increased sleep and extended lifespan. Mechanistically, early-life activation of this program is sufficient to extend lifespan, identifying synaptic remodeling as a causal driver of adaptive responses. MB-specific autophagy disruption further leads to non-cell autonomous accumulation of autophagic substrates across the brain, consistent with a system-level proteostatic imbalance in which degradative pathways remain active, but appear insufficient to match cargo load. Our findings identify autophagy in the mushroom body as a key regulator of brain-wide synaptic architecture and resilience, and establish a genetically tractable model for how local proteostatic impairment can trigger adaptive, system-level circuit remodeling.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148408389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Structure and receptor recognition of type-II feline infectious peritonitis virus spike glycoprotein.","authors":"Sheng Niu,Yuyang Tian,Linh Nguyen,Chongzhi Bai,Xiaohan Hou,Dan Wang,Ziqian Niu,Zhimin Liu,Jianle Ren,Wentao Li,Qihui Wang,Wen-Xia Tian,Junqing Sun,George Fu Gao","doi":"10.1038/s44318-026-00849-2","DOIUrl":"https://doi.org/10.1038/s44318-026-00849-2","url":null,"abstract":"Type-II feline infectious peritonitis virus (FIPV-II) is a lethal alphacoronavirus, whose high homology with the human coronavirus CCoV-HuPn-2018 carries the risk of potential zoonotic FIPV-II transmission to humans. FIPV-II infects felids using cat aminopeptidase N (cAPN) as its cell-entry receptor, but the molecular details remain unclear. Here, we resolved cryo-electron microscopy (cryo-EM) structures of the spike (S) trimer of a representative FIPV-II strain 79-1146 (FIPV-1146), and of its complex with cAPN. The reconstructions reveal structural transitions of the S protein between the \"standing\" and \"lying\" receptor-binding domain (RBD) conformation upon complex formation with cAPN in its open conformation. Structural and mutational analyses revealed that the cAPN residues R378, D751 and R779, as well as the N748-linked glycan are essential for high-affinity RBD engagement. Cross-species analysis demonstrated narrow tropism of FIPV-1146, limited to felids and canids. Introducing the N595K and Q596R substitutions found in transmissible gastroenteritis virus (TGEV) into the FIPV-1146 RBD expands its binding capacity to APNs from pig, bovine, horse and giant panda. These findings provide insights into the entry mechanism and zoonotic constraints of FIPV-II, with potential relevance for antiviral strategies against coronaviruses.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148408390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The EMBO JournalPub Date : 2026-07-07DOI: 10.1038/s44318-026-00850-9
Aashika Sekar,Alberto Rizzo,Elodie Sins,Alexander D Fulford,Lucy Silcock,Paulo S Ribeiro
{"title":"PP2A phosphatase regulates Hippo signalling in dual manner.","authors":"Aashika Sekar,Alberto Rizzo,Elodie Sins,Alexander D Fulford,Lucy Silcock,Paulo S Ribeiro","doi":"10.1038/s44318-026-00850-9","DOIUrl":"https://doi.org/10.1038/s44318-026-00850-9","url":null,"abstract":"Hippo signalling is an evolutionarily conserved pathway that regulates tissue growth. The FERM domain protein Expanded (Ex) integrates polarity cues to activate the Hippo pathway. Previous work has shown that the apicobasal polarity protein Crumbs can limit Hippo activity by promoting the phosphorylation and degradation of Ex. Here, we provide evidence that serine/threonine phosphatase, protein phosphatase 2A (PP2A) has a dual role in the regulation of Hippo signalling in Drosophila cell culture and wing discs. We show that PP2AWrd, the PP2A holoenzyme equipped with the Wrd regulatory subunit, counteracts the effects of Crumbs, by dephosphorylating and stabilising Ex. We demonstrate that the PP2AWrd holoenzyme can increase Hippo signalling activity, in contrast to the previously established Hippo pathway inhibitory role of the PP2ACka-containing STRIPAK complex. We find that the holocomplexes PP2AWrd and PP2ATws can both regulate Ex proteostasis. Remarkably, the upstream Hippo regulator, Kibra interacts with PP2AWrd and prevents Ex degradation. However, Kibra is unable to antagonise Crumbs-mediated Ex regulation, in agreement with the previously established role of Crumbs in inhibiting Kibra function. Overall, our work characterises a novel Hippo-activating role for PP2A in the stabilisation of Ex and provides new insights into how PP2A tightly controls Hippo activity in response to polarity stimuli.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148400859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The EMBO JournalPub Date : 2026-07-06DOI: 10.1038/s44318-026-00845-6
Abdullah Altulea,Sebastian Mackedenski,Jamil Nehme,Marco Demaria
{"title":"SenFlag gene signature identifies senescent cells in mouse and human tissues through a conserved core transcriptional program.","authors":"Abdullah Altulea,Sebastian Mackedenski,Jamil Nehme,Marco Demaria","doi":"10.1038/s44318-026-00845-6","DOIUrl":"https://doi.org/10.1038/s44318-026-00845-6","url":null,"abstract":"Identifying senescent cells via single-cell transcriptome profiling data remains challenging due to cellular heterogeneity and overlap with other cellular states. Here, we present SenFlag, a streamlined gene signature for enhanced identification of senescent cells based on integration of core gene expression features. SenFlag was derived through systematic assessment of bulk and single-cell RNA-sequencing datasets across multiple senescence models. It captures a conserved transcriptional program characterized by reduced expression of proliferation-associated genes and chromatin-associated genes (HMGB1/2, HMGN2), combined with upregulation of cell-cycle inhibitors (CDKN1A/CDKN2A) and of CCND1. Additionally, SenFlag incorporates lysosomal features, including increased expression of V-ATPase subunits and cathepsins. SenFlag identifies a rare but progressively accumulating population of senescent cells across tissues in both mice and humans in vivo, with enrichment in epithelial and endothelial compartments. SenFlag-positive cells increase with age and following tissue injury, and are reduced in datasets involving senescence-targeting interventions, supporting its specificity in vivo. Together, SenFlag provides a robust and interpretable signature for identifying senescent cells in single-cell datasets and facilitates the study of senescence across physiological and pathological contexts.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"65 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148393348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The TPR2 corepressor forms condensates with repressors to fine-tune growth and development in rice.","authors":"Yu Zhang,Bingchen Li,Yu Chen,Jiawei Li,Yao Wang,Tiantian Ye,Ying Ye,Zhiwei Liu,Zhiyue Feng,Stephanie Hutin,Shaoli Zhou,Jianping Guo,Ruihui Zhang,Zhu Liu,Faming Dong,Haiyan Xiong,Chloe Zubieta,Lizhong Xiong,Xuelei Lai","doi":"10.1038/s44318-026-00852-7","DOIUrl":"https://doi.org/10.1038/s44318-026-00852-7","url":null,"abstract":"Transcriptional repression is a central mechanism regulating plant growth and development, yet how plant-specific corepressors achieve robust gene silencing remains unclear. Here, we identify the rice corepressor TPR2 (TOPLESS-RELATED 2) as a phase-separating protein that forms nuclear condensates through the cooperative action of an intrinsically disordered region (IDR1) and a plant-specific N-terminal tetramerization domain. Structure-guided mutagenesis disrupting tetramerization or deleting IDR1 markedly impaired condensate formation in vivo and in vitro. Complementation assays showed that only full-length TPR2, capable of robust condensate formation, rescued the growth defects of the tpr2 mutant, whereas phase separation-deficient variants failed to do so. Mechanistically, we demonstrate that TPR2 co-condenses with repressors such as D53 and IAA3 to facilitate histone deacetylation and establish repressive chromatin states in a phase separation-dependent manner, thereby fine-tuning key developmental genes. Together, these findings define a condensate-based mechanism for transcriptional repression in plants, linking corepressor phase separation to chromatin modification, gene silencing and developmental control.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"63 11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148393349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The EMBO JournalPub Date : 2026-07-03DOI: 10.1038/s44318-026-00827-8
Rebeca Acin-Perez,Essam A Assali,Michaela Veliova,Jennifer Ngo,Alexandra J Brownstein,Francisco Villalobos,Anton Petcherski,Pablo Hernansanz-Agustin,Doyeon Kim-Vasquez,Shili Xu,Mikayla Tamboline,Raquel Maria Silva,Alexander Upcher,Cynthia Shu,Daniel E Ferriss,Marc Liesa,Jose Antonio Enriquez,Israel Sekler,Orian S Shirihai
{"title":"Mitochondrial calcium regulates lipid metabolism by modulating tethering of mitochondria to lipid droplets.","authors":"Rebeca Acin-Perez,Essam A Assali,Michaela Veliova,Jennifer Ngo,Alexandra J Brownstein,Francisco Villalobos,Anton Petcherski,Pablo Hernansanz-Agustin,Doyeon Kim-Vasquez,Shili Xu,Mikayla Tamboline,Raquel Maria Silva,Alexander Upcher,Cynthia Shu,Daniel E Ferriss,Marc Liesa,Jose Antonio Enriquez,Israel Sekler,Orian S Shirihai","doi":"10.1038/s44318-026-00827-8","DOIUrl":"https://doi.org/10.1038/s44318-026-00827-8","url":null,"abstract":"Adrenergic stimulation of brown adipocytes induces a robust detachment of mitochondria from lipid droplets (LD), which is followed by lipolysis and lipid catabolism. However, the signals inducing mitochondria attachment or detachment, and their role in lipid metabolism, remain unknown. Here, we reconstituted mitochondria-LD interaction in brown adipocyte tissue (BAT) ex vivo. We find that removal of mitochondria from lipid droplets permits higher lipolytic activity of recombinant lipases. Testing the effect of thermogenic secondary messengers and metabolites on attachment and detachment identified elevated mitochondrial matrix calcium as a potent inducer of detachment. Further, deletion of the mitochondrial sodium/calcium exchanger, NCLX, resulted in reduced attachment and increased detachment, while activation of NCLX increased attachment. We find that elevated matrix calcium causes detachment by inducing architectural transformation of peridroplet mitochondria (PDM) from their typical LD-surface-bound crescent shape into a round shape. PDE2A inhibition activates NCLX and increases PDM content in BAT in vitro and in vivo. We conclude that a surge in mitochondrial matrix calcium ions serves as a potent signal to induce mitochondrial detachment from lipid droplets, thereby facilitating lipolysis.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148379697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The EMBO JournalPub Date : 2026-07-03DOI: 10.1038/s44318-026-00843-8
Alexis T Chang,Ricard A Rodriguez-Mias,Matthew D Berg,Sophie Moggridge,Judit Villén
{"title":"Scalable phosphotyrosine enrichment with SH2 superbinder enables deep profiling of EGF responses.","authors":"Alexis T Chang,Ricard A Rodriguez-Mias,Matthew D Berg,Sophie Moggridge,Judit Villén","doi":"10.1038/s44318-026-00843-8","DOIUrl":"https://doi.org/10.1038/s44318-026-00843-8","url":null,"abstract":"Phosphotyrosine signaling plays a critical role in many biological processes, from cell proliferation to immune response. Despite its importance, proteomic studies of tyrosine phosphorylation have been limited in scale and throughput due to the need for specialized enrichment with costly reagents and labor-intensive protocols. To address these challenges, we developed R2HaPpY, a phosphotyrosine enrichment method that combines highly simplified phosphotyrosine superbinder reagent preparation and automated high-throughput enrichment. Our new reagent binds phosphotyrosine peptides at higher efficiency than other enrichment reagents and reduces both cost and preparation time by 20-fold. We generalized the R2HaPpY method to samples of low and high levels of phosphotyrosine. We benchmarked biological application to study EGF signaling dynamics in HeLa cells. Using only ~1 mg of input peptides, we detect and quantify 1651 unique phosphotyrosine sites. These include 878 regulated pY sites, many of which are novel or not previously annotated as EGF-responsive. Our results reveal differential temporal regulation and represent the largest phosphotyrosine dataset of cellular response to EGF stimulation to date. This streamlined, cost-effective, and sensitive method enables quantitative mapping of tyrosine phosphorylation dynamics at a scale of hundreds of samples, facilitating integration of phosphotyrosine signaling into multiomic studies across diverse biological systems and disease states.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148379696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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