{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nFYB1, which encodes the adhesion and degranulation‐promoting adaptor protein (ADAP), is a hematopoietic‐specific scaffold that plays a central role in immune cell activation. In T lymphocytes, ADAP is critical for transducing T cell receptor signals into the assembly of dynamic SLP‑76 microclusters, thereby enabling integrin‐mediated adhesion, stable T cell–antigen presenting cell conjugation, and downstream NF‑κB activation. In addition, ADAP contributes to cell motility and proliferation in platelets by regulating integrin activation. Those functions establish ADAP as a key facilitator of the multicellular immune response by linking receptor triggering to intracellular signaling events and cytoskeletal rearrangements."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n\nFYB1/ADAP exerts its functions through multivalent interactions. Its modular domains—notably, the hSH3 domain—mediate interactions with both signaling proteins (such as SLP‑76 and SKAP55) and directly with acidic phospholipids at the plasma membrane. A critical regulatory mechanism involves ADAP’s phosphorylation at key residues (for example, tyrosine 595), which is required for the sustained incorporation of ADAP into SLP‑76 microclusters and for the stabilization of signaling platforms that promote activation marker upregulation (e.g., CD69). Thus, through its capacity to integrate receptor-proximal events with cytoskeletal and transcriptional regulatory pathways, FYB1/ADAP is essential for orchestrating effective immune responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yanping Huang, Darrell D Norton, Patricia Precht, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Deficiency of ADAP/Fyb/SLAP-130 destabilizes SKAP55 in Jurkat T cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M413201200"}], "href": "https://doi.org/10.1074/jbc.M413201200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15849195"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15849195"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Kristen L Mueller, Molly S Thomas, Brandon J Burbach, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Adhesion and degranulation-promoting adapter protein (ADAP) positively regulates T cell sensitivity to antigen and T cell survival."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.179.6.3559"}], "href": "https://doi.org/10.4049/jimmunol.179.6.3559"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17785790"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17785790"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Rupa Srivastava, Brandon J Burbach, Yoji Shimizu "}, {"type": "b", "children": [{"type": "t", "text": "NF-kappaB activation in T cells requires discrete control of IkappaB kinase alpha/beta (IKKalpha/beta) phosphorylation and IKKgamma ubiquitination by the ADAP adapter protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.068999"}], "href": "https://doi.org/10.1074/jbc.M109.068999"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20164171"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20164171"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "C Levin, A Koren, E Pretorius, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Deleterious mutation in the FYB gene is associated with congenital autosomal recessive small-platelet thrombocytopenia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Thromb Haemost (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jth.12966"}], "href": "https://doi.org/10.1111/jth.12966"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25876182"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25876182"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Juliana B Lewis, Frank A Scangarello, Joanne M Murphy, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ADAP is an upstream regulator that precedes SLP-76 at sites of TCR engagement and stabilizes signaling microclusters."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.215517"}], "href": "https://doi.org/10.1242/jcs.215517"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30305305"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30305305"}]}]}]}