{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPI4K2B, a type II phosphatidylinositol 4‐kinase, is emerging as a multifunctional enzyme that not only contributes to the generation of phosphatidylinositol 4‐phosphate but also forms specific protein–protein interactions. Structural studies reveal that PI4K2B interacts with the catalytic–active PI4KIIα isoform—an association that modulates overall kinase activity as well as subcellular localization—and provide a high‐resolution view of its conformational features that may allow for isoform‐specific inhibitor design."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of immune cell activation, PI4K2B plays an integral role in early receptor‐mediated signaling. Evidence shows that PI4K2B associates with components of the T cell receptor complex—binding to the CD3ζ chain as well as the CD4 receptor—in a tyrosine phosphorylation–dependent manner, thereby facilitating intracellular calcium release and cytoskeletal reorganization necessary for T cell activation. Its recruitment to the FcεRIγ chain in mast cells further underscores its importance in transducing signals following immune receptor ligation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond classical receptor signaling, PI4K2B is implicated in specialized cellular processes. In endothelial cells, its activity is critical for the biogenesis of Weibel–Palade bodies—organelles that store and regulate the release of von Willebrand factor—thus impacting haemostatic function. Moreover, a variant of PI4K2B, LB-PI4K2B-1S, has been identified as an autosomal minor histocompatibility antigen that can be targeted by CD4⁺ T cells following allogeneic stem cell transplantation, highlighting a role in immune surveillance. Intriguingly, genetic association studies have also implicated PI4K2B as a candidate susceptibility gene in psychiatric disorders such as schizophrenia."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yvette Bultsma, Willem-Jan Keune, Nullin Divecha "}, {"type": "b", "children": [{"type": "t", "text": "PIP4Kbeta interacts with and modulates nuclear localization of the high-activity PtdIns5P-4-kinase isoform PIP4Kalpha."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20100341"}], "href": "https://doi.org/10.1042/BJ20100341"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20583997"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20583997"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Martin Klima, Adriana Baumlova, Dominika Chalupska, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The high-resolution crystal structure of phosphatidylinositol 4-kinase IIβ and the crystal structure of phosphatidylinositol 4-kinase IIα containing a nucleoside analogue provide a structural basis for isoform-specific inhibitor design."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Crystallogr D Biol Crystallogr (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1107/S1399004715009505"}], "href": "https://doi.org/10.1107/S1399004715009505"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26143926"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26143926"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Rupa Srivastava, Ranjeet K Sinha, Gosukonda Subrahmanyam "}, {"type": "b", "children": [{"type": "t", "text": "Type II phosphatidylinositol 4-kinase beta associates with TCR-CD3 zeta chain in Jurkat cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Immunol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molimm.2005.03.009"}], "href": "https://doi.org/10.1016/j.molimm.2005.03.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16337488"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16337488"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ranjeet K Sinha, Naveen Bojjireddy, Dakshayini Kulkarni, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Type II phosphatidylinositol 4-kinase β is an integral signaling component of early T cell activation mechanisms."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochimie (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biochi.2013.04.005"}], "href": "https://doi.org/10.1016/j.biochi.2013.04.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23619705"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23619705"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Ranjeet Kumar Sinha, Naveen Bojjireddy, Deepak Kanojia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Type II PtdIns 4-kinase β associates with CD4-p56lck complex and is involved in CD4 receptor signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biochem (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11010-014-2129-9"}], "href": "https://doi.org/10.1007/s11010-014-2129-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24972704"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24972704"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Naveen Bojjireddy, Ranjeet Kumar Sinha, Gosukonda Subrahmanyam "}, {"type": "b", "children": [{"type": "t", "text": "Type II phosphatidylinositol 4-kinases interact with FcεRIγ subunit in RBL-2H3 cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biochem (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11010-014-1970-1"}], "href": "https://doi.org/10.1007/s11010-014-1970-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24481753"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24481753"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Mafalda Lopes da Silva, Marie N O'Connor, Janos Kriston-Vizi, et al. 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