{"entity": "journal", "iuid": "1422a49654a54877981959cd796046df", "timestamp": "2026-06-17T03:45:38.703Z", "links": {"self": {"href": "https://publications.scilifelab.se/journal/Sci%20Signal.json"}, "display": {"href": "https://publications.scilifelab.se/journal/Sci%20Signal"}}, "title": "Sci Signal", "issn": "1937-9145", "issn-l": "1945-0877", "publications_count": 7, "publications": [{"entity": "publication", "iuid": "a175614cbb35435b95c49b60a97d3873", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a175614cbb35435b95c49b60a97d3873.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a175614cbb35435b95c49b60a97d3873"}}, "title": "SHP-1 localization to the activating immune synapse promotes NK cell tolerance in MHC class I deficiency.", "authors": [{"family": "Schmied", "given": "Laurent", "initials": "L", "orcid": "0000-0002-3303-881X", "researcher": {"href": "https://publications.scilifelab.se/researcher/cfc51f1c9baf46b9acb5fc93a10f2ec0.json"}}, {"family": "Luu", "given": "Thuy T", "initials": "TT", "orcid": "0000-0002-2619-1357", "researcher": {"href": "https://publications.scilifelab.se/researcher/1175414483ac4ae89613bd7d97f8bde3.json"}}, {"family": "S\u00f8ndergaard", "given": "Jonas N", "initials": "JN", "orcid": "0000-0002-4438-6756", "researcher": {"href": "https://publications.scilifelab.se/researcher/d0125f039a4949d8a22b9048d7f6b7d8.json"}}, {"family": "Hald", "given": "Sophia H", "initials": "SH"}, {"family": "Meinke", "given": "Stephan", "initials": "S", "orcid": "0000-0003-4489-9727", "researcher": {"href": "https://publications.scilifelab.se/researcher/56e4d4a720d94731b5706397ac11d0a1.json"}}, {"family": "Mohammad", "given": "Dara K", "initials": "DK", "orcid": "0000-0001-9201-0991", "researcher": {"href": "https://publications.scilifelab.se/researcher/57007b9b1bea4fbeba66f8931a87293d.json"}}, {"family": "Singh", "given": "Sunitha B", "initials": "SB", "orcid": "0000-0002-2812-545X", "researcher": {"href": "https://publications.scilifelab.se/researcher/75549893113643e9a031aed5599a691a.json"}}, {"family": "Mayer", "given": "Corinna", "initials": "C"}, {"family": "Perinetti Casoni", "given": "Giovanna", "initials": "G", "orcid": "0000-0002-1729-889X", "researcher": {"href": "https://publications.scilifelab.se/researcher/943709e564a24fbb8b99ae9f71208dd7.json"}}, {"family": "Chrobok", "given": "Michael", "initials": "M"}, {"family": "Schlums", "given": "Heinrich", "initials": "H", "orcid": "0000-0002-2895-7766", "researcher": {"href": "https://publications.scilifelab.se/researcher/3519af1c1eae4ffcb381a420c052ac28.json"}}, {"family": "Rota", "given": "Giorgia", "initials": "G"}, {"family": "Truong", "given": "Hieu M", "initials": "HM"}, {"family": "Westerberg", "given": "Lisa S", "initials": "LS", "orcid": "0000-0003-2943-2192", "researcher": {"href": "https://publications.scilifelab.se/researcher/9ec4551066bb40c1bad6c3fd9224be2e.json"}}, {"family": "Guarda", "given": "Greta", "initials": "G", "orcid": "0000-0001-9243-6116", "researcher": {"href": "https://publications.scilifelab.se/researcher/aa75e90a48034de990913d5aebd954ef.json"}}, {"family": "Alici", "given": "Evren", "initials": "E", "orcid": "0000-0001-5307-6648", "researcher": {"href": "https://publications.scilifelab.se/researcher/94af705a738741dd928e90fe403b9475.json"}}, {"family": "Wagner", "given": "Arnika K", "initials": "AK", "orcid": "0000-0002-0339-8259", "researcher": {"href": "https://publications.scilifelab.se/researcher/8dd10981a93a490b940ca41d2bde96a3.json"}}, {"family": "Kadri", "given": "Nadir", "initials": "N", "orcid": "0000-0003-2623-4094", "researcher": {"href": "https://publications.scilifelab.se/researcher/70724b181f324c7aac42468a177dcff4.json"}}, {"family": "Bryceson", "given": "Yenan T", "initials": "YT", "orcid": "0000-0002-7783-9934", "researcher": {"href": "https://publications.scilifelab.se/researcher/ce63349a03924444836215ffd201d2e3.json"}}, {"family": "Saeed", "given": "Mezida B", "initials": "MB"}, {"family": "H\u00f6glund", "given": "Petter", "initials": "P", "orcid": "0000-0002-9233-626X", "researcher": {"href": "https://publications.scilifelab.se/researcher/d7c852c7cc0043b88fa096adf6af92dd.json"}}], "type": "journal article", "published": "2023-04-11", "journal": {"title": "Sci Signal", "issn": "1937-9145", "volume": "16", "issue": "780", "pages": "eabq0752", "issn-l": "1945-0877"}, "abstract": "Natural killer (NK) cells recognize virally infected cells and tumors. NK cell function depends on balanced signaling from activating receptors, recognizing products from tumors or viruses, and inhibitory receptors (such as KIR/Ly49), which recognize major histocompatibility complex class I (MHC-I) molecules. KIR/Ly49 signaling preserves tolerance to self but also conveys reactivity toward MHC-I-low target cells in a process known as NK cell education. Here, we found that NK cell tolerance and education were determined by the subcellular localization of the tyrosine phosphatase SHP-1. In mice lacking MHC-I molecules, uneducated, self-tolerant Ly49A+ NK cells showed accumulation of SHP-1 in the activating immune synapse, where it colocalized with F-actin and the signaling adaptor protein SLP-76. Education of Ly49A+ NK cells by the MHC-I molecule H2Dd led to reduced synaptic accumulation of SHP-1, accompanied by augmented signaling from activating receptors. Education was also linked to reduced transcription of Ptpn6, which encodes SHP-1. Moreover, synaptic SHP-1 accumulation was reduced in NK cells carrying the H2Dd-educated receptor Ly49G2 but not in those carrying the noneducating receptor Ly49I. Colocalization of Ly49A and SHP-1 outside of the synapse was more frequent in educated compared with uneducated NK cells, suggesting a role for Ly49A in preventing synaptic SHP-1 accumulation in NK cell education. Thus, distinct patterning of SHP-1 in the activating NK cell synapse may determine NK cell tolerance.", "doi": "10.1126/scisignal.abq0752", "pmid": "37040441", "labels": {"Integrated Microscopy Technologies Stockholm": "Service"}, "xrefs": [], "notes": [], "created": "2023-04-16T19:22:34.118Z", "modified": "2023-04-16T19:22:34.444Z"}, {"entity": "publication", "iuid": "d4607c3b5d1647179a3ed651e6923fa2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d4607c3b5d1647179a3ed651e6923fa2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d4607c3b5d1647179a3ed651e6923fa2"}}, "title": "Clearance of small intestinal crypts involves goblet cell mucus secretion by intracellular granule rupture and enterocyte ion transport.", "authors": [{"family": "Dolan", "given": "Brendan", "initials": "B", "orcid": "0000-0001-9062-3882", "researcher": {"href": "https://publications.scilifelab.se/researcher/6ff7d8f515ef4707ab6bca8da108f115.json"}}, {"family": "Ermund", "given": "Anna", "initials": "A", "orcid": "0000-0002-3233-043X", "researcher": {"href": "https://publications.scilifelab.se/researcher/8215eeb434f84deaafa2f9f198bfb2bc.json"}}, {"family": "Martinez-Abad", "given": "Beatriz", "initials": "B", "orcid": "0000-0002-0521-3473", "researcher": {"href": "https://publications.scilifelab.se/researcher/2d3781ca1b0245908c2030b4707cc34d.json"}}, {"family": "Johansson", "given": "Malin E V", "initials": "MEV", "orcid": "0000-0002-4237-6677", "researcher": {"href": "https://publications.scilifelab.se/researcher/520dab35c19049c8b3f1083a92e60d56.json"}}, {"family": "Hansson", "given": "Gunnar C", "initials": "GC", "orcid": "0000-0002-1900-1869", "researcher": {"href": "https://publications.scilifelab.se/researcher/44b3815603154322a6dac16f2fc1c1e9.json"}}], "type": "journal article", "published": "2022-09-20", "journal": {"title": "Sci Signal", "issn": "1937-9145", "volume": "15", "issue": "752", "pages": "eabl5848", "issn-l": "1945-0877"}, "abstract": "Goblet cells in the small intestinal crypts contain large numbers of mucin granules that are rapidly discharged to clean bacteria from the crypt. Because acetylcholine released by neuronal and nonneuronal cells controls many aspects of intestinal epithelial function, we used tissue explants and organoids to investigate the response of the small intestinal crypt to cholinergic stimulation. The activation of muscarinic acetylcholine receptors initiated a coordinated and rapid emptying of crypt goblet cells that flushed the crypt contents into the intestinal lumen. Cholinergic stimulation induced an expansion of the granule contents followed by intracellular rupture of the mucin granules. The mucus expanded intracellularly before the rupture of the goblet cell apical membrane and continued to expand after its release into the crypt lumen. The goblet cells recovered from membrane rupture and replenished their stores of mucin granules. Mucus secretion from the goblet cells depended on Ca2+ signaling and the expansion of the mucus in the crypt depended on gap junctions and on ion and water transport by enterocytes adjacent to the goblet cells. This distinctive mode of mucus secretion, which we refer to as \"expanding secretion,\" efficiently cleans the small intestine crypt through coordinated mucus, ion, and fluid secretion by goblet cells and enterocytes.", "doi": "10.1126/scisignal.abl5848", "pmid": "36126118", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "mid", "key": "NIHMS1851593"}, {"db": "pmc", "key": "PMC9749883"}], "notes": [], "created": "2023-02-16T08:26:10.686Z", "modified": "2023-02-16T08:26:10.773Z"}, {"entity": "publication", "iuid": "836d8b1e7ef94eb782ad4e2c1653e47a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/836d8b1e7ef94eb782ad4e2c1653e47a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/836d8b1e7ef94eb782ad4e2c1653e47a"}}, "title": "NK cells integrate signals over large areas when building immune synapses but require local stimuli for degranulation.", "authors": [{"family": "Verron", "given": "Quentin", "initials": "Q", "orcid": "0000-0001-5800-4379", "researcher": {"href": "https://publications.scilifelab.se/researcher/a961009c75cf42499996cfd89e7c46e5.json"}}, {"family": "Forslund", "given": "Elin", "initials": "E"}, {"family": "Brandt", "given": "Ludwig", "initials": "L", "orcid": "0000-0003-2040-3176", "researcher": {"href": "https://publications.scilifelab.se/researcher/a1683a18701c4e23ad7005a6672595f9.json"}}, {"family": "Leino", "given": "Mattias", "initials": "M", "orcid": "0000-0002-7533-043X", "researcher": {"href": "https://publications.scilifelab.se/researcher/88c2bd6f902f4b8c96a1855ab4bf12ab.json"}}, {"family": "Frisk", "given": "Thomas W", "initials": "TW", "orcid": "0000-0002-3996-9279", "researcher": {"href": "https://publications.scilifelab.se/researcher/c8a1aeeab11e4180afd6551faf16ab9f.json"}}, {"family": "Olofsson", "given": "Per E", "initials": "PE", "orcid": "0000-0002-6019-8157", "researcher": {"href": "https://publications.scilifelab.se/researcher/204c5891e333412cab14381b853c49a4.json"}}, {"family": "\u00d6nfelt", "given": "Bj\u00f6rn", "initials": "B", "orcid": "0000-0001-5178-7593", "researcher": {"href": "https://publications.scilifelab.se/researcher/14bcdcf94cab40ff92319869d243f5d8.json"}}], "type": "journal article", "published": "2021-05-25", "journal": {"title": "Sci Signal", "issn": "1937-9145", "issn-l": "1945-0877", "volume": "14", "issue": "684", "pages": "eabe2740"}, "abstract": "Immune synapses are large-scale, transient molecular assemblies that serve as platforms for antigen presentation to B and T cells and for target recognition by cytotoxic T cells and natural killer (NK) cells. The formation of an immune synapse is a tightly regulated, stepwise process in which the cytoskeleton, cell surface receptors, and intracellular signaling proteins rearrange into supramolecular activation clusters (SMACs). We generated artificial immune synapses (AIS) consisting of synthetic and natural ligands for the NK cell-activating receptors LFA-1 and CD16 by microcontact printing the ligands into circular-shaped SMAC structures. Live-cell imaging and analysis of fixed human NK cells in this reductionist system showed that the spatial distribution of activating ligands influenced the formation, stability, and outcome of NK cell synapses. Whereas engagement of LFA-1 alone promoted synapse initiation, combined engagement of LFA-1 and CD16 was required for the formation of mature synapses and degranulation. Organizing LFA-1 and CD16 ligands into donut-shaped AIS resulted in fewer long-lasting, symmetrical synapses compared to dot-shaped AIS. NK cells spreading evenly over either AIS shape exhibited similar arrangements of the lytic machinery. However, degranulation only occurred in regions containing ligands that therefore induced local signaling, suggesting the existence of a late checkpoint for degranulation. Our results demonstrate that the spatial organization of ligands in the synapse can affect its outcome, which could be exploited by target cells as an escape mechanism.", "doi": "10.1126/scisignal.abe2740", "pmid": "34035142", "labels": {"Integrated Microscopy Technologies Stockholm": "Service"}, "xrefs": [{"db": "pii", "key": "14/684/eabe2740"}], "notes": [], "created": "2021-05-26T07:17:06.650Z", "modified": "2021-11-10T12:24:36.755Z"}, {"entity": "publication", "iuid": "36235e9dc3c244d7a5646615de05fe18", "links": {"self": {"href": "https://publications.scilifelab.se/publication/36235e9dc3c244d7a5646615de05fe18.json"}, "display": {"href": "https://publications.scilifelab.se/publication/36235e9dc3c244d7a5646615de05fe18"}}, "title": "An atlas of human metabolism.", "authors": [{"family": "Robinson", "given": "Jonathan L", "initials": "JL", "orcid": "0000-0001-8567-5960", "researcher": {"href": "https://publications.scilifelab.se/researcher/b70b6d9b64fd45e882c4108aded013d4.json"}}, {"family": "Kocaba\u015f", "given": "P\u0131nar", "initials": "P", "orcid": "0000-0001-9788-2019", "researcher": {"href": "https://publications.scilifelab.se/researcher/c89eb03e619945a2a2058179b0d0e310.json"}}, {"family": "Wang", "given": "Hao", "initials": "H", "orcid": "0000-0001-7475-0136", "researcher": {"href": "https://publications.scilifelab.se/researcher/836b4fbf7ebd4f80abc84465c8f29a2e.json"}}, {"family": "Cholley", "given": "Pierre-Etienne", "initials": "PE"}, {"family": "Cook", "given": "Daniel", "initials": "D", "orcid": "0000-0001-5534-8600", "researcher": {"href": "https://publications.scilifelab.se/researcher/ad0b42774a1e4e0580dde05e95fcb1fc.json"}}, {"family": "Nilsson", "given": "Avlant", "initials": "A", "orcid": "0000-0002-9476-4516", "researcher": {"href": "https://publications.scilifelab.se/researcher/44da161dba604c9e803a4af303277083.json"}}, {"family": "Anton", "given": "Mihail", "initials": "M", "orcid": "0000-0002-7753-9042", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a28ecc2261e436ea5884ada5e512aed.json"}}, {"family": "Ferreira", "given": "Raphael", "initials": "R", "orcid": "0000-0001-9881-6232", "researcher": {"href": "https://publications.scilifelab.se/researcher/5e97f22759cd4e008d9b6473f52865e5.json"}}, {"family": "Domenzain", "given": "Iv\u00e1n", "initials": "I", "orcid": "0000-0002-5322-2040", "researcher": {"href": "https://publications.scilifelab.se/researcher/3793e87625584ee2a31301297263a12a.json"}}, {"family": "Billa", "given": "Virinchi", "initials": "V"}, {"family": "Limeta", "given": "Angelo", "initials": "A"}, {"family": "Hedin", "given": "Alex", "initials": "A", "orcid": "0000-0002-0829-2496", "researcher": {"href": "https://publications.scilifelab.se/researcher/88756d4d3b894ab288141af7b9c9b052.json"}}, {"family": "Gustafsson", "given": "Johan", "initials": "J", "orcid": "0000-0001-5072-2659", "researcher": {"href": "https://publications.scilifelab.se/researcher/bd5fda1ac79e49c185ba6f4dfcdff5fc.json"}}, {"family": "Kerkhoven", "given": "Eduard J", "initials": "EJ", "orcid": "0000-0002-3593-5792", "researcher": {"href": "https://publications.scilifelab.se/researcher/0df361f8014144e79479631fcbffad53.json"}}, {"family": "Svensson", "given": "L Thomas", "initials": "LT", "orcid": "0000-0002-9190-2979", "researcher": {"href": "https://publications.scilifelab.se/researcher/dc636683ece84dc4ac3e4d10df0c7a49.json"}}, {"family": "Palsson", "given": "Bernhard O", "initials": "BO", "orcid": "0000-0003-2357-6785", "researcher": {"href": "https://publications.scilifelab.se/researcher/b72eed29485a433cb85e260ee38dc894.json"}}, {"family": "Mardinoglu", "given": "Adil", "initials": "A", "orcid": "0000-0002-4254-6090", "researcher": {"href": "https://publications.scilifelab.se/researcher/da756265658c4ed2a8911644583e07a3.json"}}, {"family": "Hansson", "given": "Lena", "initials": "L"}, {"family": "Uhl\u00e9n", "given": "Mathias", "initials": "M", "orcid": "0000-0002-4858-8056", "researcher": {"href": "https://publications.scilifelab.se/researcher/ff81da3cb0cf4262873b993a1b06798c.json"}}, {"family": "Nielsen", "given": "Jens", "initials": "J", "orcid": "0000-0002-9955-6003", "researcher": {"href": "https://publications.scilifelab.se/researcher/7a596e289be4438a8a2653b1f25fea8b.json"}}], "type": "journal article", "published": "2020-03-24", "journal": {"title": "Sci Signal", "issn": "1937-9145", "issn-l": "1945-0877", "volume": "13", "issue": "624", "pages": null}, "abstract": "Genome-scale metabolic models (GEMs) are valuable tools to study metabolism and provide a scaffold for the integrative analysis of omics data. Researchers have developed increasingly comprehensive human GEMs, but the disconnect among different model sources and versions impedes further progress. We therefore integrated and extensively curated the most recent human metabolic models to construct a consensus GEM, Human1. We demonstrated the versatility of Human1 through the generation and analysis of cell- and tissue-specific models using transcriptomic, proteomic, and kinetic data. We also present an accompanying web portal, Metabolic Atlas (https://www.metabolicatlas.org/), which facilitates further exploration and visualization of Human1 content. Human1 was created using a version-controlled, open-source model development framework to enable community-driven curation and refinement. This framework allows Human1 to be an evolving shared resource for future studies of human health and disease.", "doi": "10.1126/scisignal.aaz1482", "pmid": "32209698", "labels": {"Systems Biology": "Technology development", "Bioinformatics Support, Infrastructure and Training": "Technology development", "Bioinformatics (NBIS)": "Technology development"}, "xrefs": [{"db": "pii", "key": "13/624/eaaz1482"}, {"db": "pmc", "key": "PMC7331181"}, {"db": "mid", "key": "NIHMS1590510"}], "notes": [], "created": "2020-12-10T11:11:44.807Z", "modified": "2021-11-10T12:52:52.282Z"}, {"entity": "publication", "iuid": "680565f978934fedb42fa5ba80bbc4fe", "links": {"self": {"href": "https://publications.scilifelab.se/publication/680565f978934fedb42fa5ba80bbc4fe.json"}, "display": {"href": "https://publications.scilifelab.se/publication/680565f978934fedb42fa5ba80bbc4fe"}}, "title": "The ALK-1/SMAD/ATOH8 axis attenuates hypoxic responses and protects against the development of pulmonary arterial hypertension.", "authors": [{"family": "Morikawa", "given": "Masato", "initials": "M", "orcid": "0000-0002-6191-7176", "researcher": {"href": "https://publications.scilifelab.se/researcher/7ff787ffdf444850b9e4906c8c95fa92.json"}}, {"family": "Mitani", "given": "Yoshihide", "initials": "Y"}, {"family": "Holmborn", "given": "Katarina", "initials": "K"}, {"family": "Kato", "given": "Taichi", "initials": "T", "orcid": "0000-0001-7084-4565", "researcher": {"href": "https://publications.scilifelab.se/researcher/a737a920309943d48f55ccbedd02fd6c.json"}}, {"family": "Koinuma", "given": "Daizo", "initials": "D", "orcid": "0000-0001-5611-2122", "researcher": {"href": "https://publications.scilifelab.se/researcher/cf10583b944248b19c07772a0b364684.json"}}, {"family": "Maruyama", "given": "Junko", "initials": "J"}, {"family": "Vasilaki", "given": "Eleftheria", "initials": "E", "orcid": "0000-0001-6743-8523", "researcher": {"href": "https://publications.scilifelab.se/researcher/9b2aa70aa68a48f7870b664caf9ca3b3.json"}}, {"family": "Sawada", "given": "Hirofumi", "initials": "H", "orcid": "0000-0001-8069-5751", "researcher": {"href": "https://publications.scilifelab.se/researcher/cf45576856c9452888d08842b88669ca.json"}}, {"family": "Kobayashi", "given": "Mai", "initials": "M"}, {"family": "Ozawa", "given": "Takayuki", "initials": "T"}, {"family": "Morishita", "given": "Yasuyuki", "initials": "Y"}, {"family": "Bessho", "given": "Yasumasa", "initials": "Y"}, {"family": "Maeda", "given": "Shingo", "initials": "S", "orcid": "0000-0002-2737-3902", "researcher": {"href": "https://publications.scilifelab.se/researcher/152d321d11944b3ca9eb3ef387e70cd0.json"}}, {"family": "Ledin", "given": "Johan", "initials": "J", "orcid": "0000-0002-7319-7735", "researcher": {"href": "https://publications.scilifelab.se/researcher/92e482abc18c49d881d3bf0132b3fbcd.json"}}, {"family": "Aburatani", "given": "Hiroyuki", "initials": "H", "orcid": "0000-0003-0438-1544", "researcher": {"href": "https://publications.scilifelab.se/researcher/5bce060d4ff8446dbafc86bf5e3a001d.json"}}, {"family": "Kageyama", "given": "Ryoichiro", "initials": "R"}, {"family": "Maruyama", "given": "Kazuo", "initials": "K", "orcid": "0000-0003-3685-6348", "researcher": {"href": "https://publications.scilifelab.se/researcher/dd2eaad9217344a89fcc666951831e75.json"}}, {"family": "Heldin", "given": "Carl-Henrik", "initials": "CH", "orcid": "0000-0002-9508-896X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f705f7c509904a1db721ace2267ca48f.json"}}, {"family": "Miyazono", "given": "Kohei", "initials": "K", "orcid": "0000-0001-7341-0172", "researcher": {"href": "https://publications.scilifelab.se/researcher/7a14a58f628d435a94ad9540478117cb.json"}}], "type": "journal article", "published": "2019-11-12", "journal": {"title": "Sci Signal", "issn": "1937-9145", "volume": "12", "issue": "607", "pages": "eaay4430", "issn-l": "1945-0877"}, "abstract": "Dysregulated bone morphogenetic protein (BMP) signaling in endothelial cells (ECs) is implicated in vascular diseases such as pulmonary arterial hypertension (PAH). Here, we showed that the transcription factor ATOH8 was a direct target of SMAD1/5 and was induced in a manner dependent on BMP but independent of Notch, another critical signaling pathway in ECs. In zebrafish and mice, inactivation of Atoh8 did not cause an arteriovenous malformation-like phenotype, which may arise because of dysregulated Notch signaling. In contrast, Atoh8-deficient mice exhibited a phenotype mimicking PAH, which included increased pulmonary arterial pressure and right ventricular hypertrophy. Moreover, ATOH8 expression was decreased in PAH patient lungs. We showed that in cells, ATOH8 interacted with hypoxia-inducible factor 2\u03b1 (HIF-2\u03b1) and decreased its abundance, leading to reduced induction of HIF-2\u03b1 target genes in response to hypoxia. Together, these findings suggest that the BMP receptor type II/ALK-1/SMAD/ATOH8 axis may attenuate hypoxic responses in ECs in the pulmonary circulation and may help prevent the development of PAH.", "doi": "10.1126/scisignal.aay4430", "pmid": "31719172", "labels": {"Genome Engineering Zebrafish": "Collaborative"}, "xrefs": [{"db": "pii", "key": "12/607/eaay4430"}, {"db": "pmc", "key": "PMC6908447"}, {"db": "mid", "key": "EMS85032"}], "notes": [], "created": "2019-12-02T16:11:40.604Z", "modified": "2021-06-16T16:18:32.543Z"}, {"entity": "publication", "iuid": "13ad7bd3b71d4d7ea7e2ccdb219db87f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/13ad7bd3b71d4d7ea7e2ccdb219db87f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/13ad7bd3b71d4d7ea7e2ccdb219db87f"}}, "title": "Pleiotrophin promotes vascular abnormalization in gliomas and correlates with poor survival in patients with astrocytomas.", "authors": [{"family": "Zhang", "given": "Lei", "initials": "L"}, {"family": "Kundu", "given": "Soumi", "initials": "S"}, {"family": "Feenstra", "given": "Tjerk", "initials": "T"}, {"family": "Li", "given": "Xiujuan", "initials": "X"}, {"family": "Jin", "given": "Chuan", "initials": "C"}, {"family": "Laaniste", "given": "Liisi", "initials": "L"}, {"family": "El Hassan", "given": "Tamador Elsir Abu", "initials": "TE"}, {"family": "Ohlin", "given": "K Elisabet", "initials": "KE"}, {"family": "Yu", "given": "Di", "initials": "D"}, {"family": "Olofsson", "given": "Tommie", "initials": "T"}, {"family": "Olsson", "given": "Anna-Karin", "initials": "AK"}, {"family": "Pont\u00e9n", "given": "Fredrik", "initials": "F"}, {"family": "Magnusson", "given": "Peetra U", "initials": "PU"}, {"family": "Nilsson", "given": "Karin Forsberg", "initials": "KF"}, {"family": "Essand", "given": "Magnus", "initials": "M"}, {"family": "Smits", "given": "Anja", "initials": "A"}, {"family": "Dieterich", "given": "Lothar C", "initials": "LC"}, {"family": "Dimberg", "given": "Anna", "initials": "A"}], "type": "journal article", "published": "2015-12-08", "journal": {"title": "Sci Signal", "issn": "1937-9145", "volume": "8", "issue": "406", "pages": "ra125", "issn-l": "1945-0877"}, "abstract": "Glioblastomas are aggressive astrocytomas characterized by endothelial cell proliferation and abnormal vasculature, which can cause brain edema and increase patient morbidity. We identified the heparin-binding cytokine pleiotrophin as a driver of vascular abnormalization in glioma. Pleiotrophin abundance was greater in high-grade human astrocytomas and correlated with poor survival. Anaplastic lymphoma kinase (ALK), which is a receptor that is activated by pleiotrophin, was present in mural cells associated with abnormal vessels. Orthotopically implanted gliomas formed from GL261 cells that were engineered to produce pleiotrophin showed increased microvessel density and enhanced tumor growth compared with gliomas formed from control GL261 cells. The survival of mice with pleiotrophin-producing gliomas was shorter than that of mice with gliomas that did not produce pleiotrophin. Vessels in pleiotrophin-producing gliomas were poorly perfused and abnormal, a phenotype that was associated with increased deposition of vascular endothelial growth factor (VEGF) in direct proximity to the vasculature. The growth of pleiotrophin-producing GL261 gliomas was inhibited by treatment with the ALK inhibitor crizotinib, the ALK inhibitor ceritinib, or the VEGF receptor inhibitor cediranib, whereas control GL261 tumors did not respond to either inhibitor. Our findings link pleiotrophin abundance in gliomas with survival in humans and mice, and show that pleiotrophin promotes glioma progression through increased VEGF deposition and vascular abnormalization.", "doi": "10.1126/scisignal.aaa1690", "pmid": "26645582", "labels": {"Tissue Profiling": "Collaborative"}, "xrefs": [{"db": "pii", "key": "8/406/ra125"}], "notes": [], "created": "2017-11-05T12:55:08.680Z", "modified": "2017-11-05T12:55:08.696Z"}, {"entity": "publication", "iuid": "a8606ec944474ea6978ada299d0a0417", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a8606ec944474ea6978ada299d0a0417.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a8606ec944474ea6978ada299d0a0417"}}, "title": "SUMOylation mediates the nuclear translocation and signaling of the IGF-1 receptor.", "authors": [{"family": "Sehat", "given": "Bita", "initials": "B"}, {"family": "Tofigh", "given": "Ali", "initials": "A"}, {"family": "Lin", "given": "Yingbo", "initials": "Y"}, {"family": "Trocm\u00e9", "given": "Eric", "initials": "E"}, {"family": "Liljedahl", "given": "Ulrika", "initials": "U", "orcid": "0000-0002-1250-392X", "researcher": {"href": "https://publications.scilifelab.se/researcher/241618974ae142b38e5fe84236819f2b.json"}}, {"family": "Lagergren", "given": "Jens", "initials": "J"}, {"family": "Larsson", "given": "Olle", "initials": "O"}], "type": "journal article", "published": "2010-02-09", "journal": {"title": "Sci Signal", "issn": "1937-9145", "issn-l": "1945-0877", "volume": "3", "issue": "108", "pages": "ra10"}, "abstract": "The insulin-like growth factor 1 receptor (IGF-1R) plays crucial roles in developmental and cancer biology. Most of its biological effects have been ascribed to its tyrosine kinase activity, which propagates signaling through the phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways. Here, we report that IGF-1 promotes the modification of IGF-1R by small ubiquitin-like modifier protein-1 (SUMO-1) and its translocation to the nucleus. Nuclear IGF-1R associated with enhancer-like elements and increased transcription in reporter assays. The SUMOylation sites of IGF-1R were identified as three evolutionarily conserved lysine residues-Lys(1025), Lys(1100), and Lys(1120)-in the beta subunit of the receptor. Mutation of these SUMO-1 sites abolished the ability of IGF-1R to translocate to the nucleus and activate transcription but did not alter its kinase-dependent signaling. Thus, we demonstrate a SUMOylation-mediated mechanism of IGF-1R signaling that has potential implications for gene regulation.", "doi": "10.1126/scisignal.2000628", "pmid": "20145208", "labels": {"National Genomics Infrastructure": "Collaborative", "NGI Uppsala (SNP&SEQ Technology Platform)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "3/108/ra10"}], "notes": [], "created": "2017-05-04T15:00:39.225Z", "modified": "2022-03-31T15:22:33.212Z"}], "created": "2017-05-09T09:12:54.573Z", "modified": "2020-11-27T13:14:08.229Z"}