{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRASAL3 is a Ras GTPase-activating protein that plays an essential role in fine‐tuning Ras/Erk signaling across various immune cell types. In NKT cells, for example, RASAL3 limits Ras activation so that its deficiency leads to hyperphosphorylation of Erk and altered cytokine production upon stimulus, thereby affecting cell expansion and function in the liver."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn T cells, RASAL3 is critical for maintaining peripheral T cell homeostasis. Although thymic development remains intact in its absence, RASAL3 deficiency impairs the survival of naive T cells, resulting in reduced T cell numbers and increased apoptosis. In addition, even activated T cells rely on RASAL3 to control cell death, as diminished Bcl2 expression and altered inflammatory responses are observed without proper Ras regulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in lymphocytes, RASAL3 serves as a key negative regulator of the Ras pathway in innate immune cells as well. In neutrophils, RASAL3 expression is upregulated following inflammatory stimuli to mitigate excessive activation and prevent hyperinflammatory responses that can lead to organ damage and increased mortality during septic shock."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Moreover, within dendritic cells, RASAL3 interacts physically and functionally with the scaffold protein CCDC88B and the guanine nucleotide exchange factor ARHGEF2. This complex modulates RHOA activation and, in doing so, differentially regulates cellular migration, which is crucial for effective immune surveillance and responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Suguru Saito, Toshihiko Kawamura, Masaya Higuchi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RASAL3, a novel hematopoietic RasGAP protein, regulates the number and functions of NKT cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Immunol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/eji.201444977"}], "href": "https://doi.org/10.1002/eji.201444977"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25652366"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25652366"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ryunosuke Muro, Takeshi Nitta, Toshiyuki Okada, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Ras GTPase-activating protein Rasal3 supports survival of naive T cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0119898"}], "href": "https://doi.org/10.1371/journal.pone.0119898"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25793935"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25793935"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ryunosuke Muro, Takeshi Nitta, Masayuki Kitajima, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rasal3-mediated T cell survival is essential for inflammatory responses."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2017.12.159"}], "href": "https://doi.org/10.1016/j.bbrc.2017.12.159"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29291408"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29291408"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Suguru Saito, Duo-Yao Cao, Aaron R Victor, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RASAL3 Is a Putative RasGAP Modulating Inflammatory Response by Neutrophils."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Immunol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fimmu.2021.744300"}], "href": "https://doi.org/10.3389/fimmu.2021.744300"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34777356"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34777356"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jean-Frederic Olivier, David Langlais, Thiviya Jeyakumar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CCDC88B interacts with RASAL3 and ARHGEF2 and regulates dendritic cell function in neuroinflammation and colitis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Commun Biol (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s42003-023-05751-9"}], "href": "https://doi.org/10.1038/s42003-023-05751-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38200184"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38200184"}]}]}]}