{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSyk functions as a critical mediator of innate immune responses by linking receptor engagement to downstream signaling events that regulate inflammation, phagocytosis, and pathogen uptake. It is activated by oxidative stress to trigger NF‐κB signaling without classical IκBα degradation (12711606), and it couples with adhesion receptors such as PSGL-1 via ERM adaptor proteins to promote SRE-dependent transcription (12387735). Syk is recruited in neutrophils upon LPS stimulation to induce selective chemokine production (14699155) and is indispensable for the signaling cascades initiated by pattern‐recognition receptors such as Dectin-1, which—depending on the context—can drive reactive oxygen production in macrophages (15956283) or lead to canonical NF‐κB activation in dendritic cells (19122653). In addition, Syk regulates endocytic events; it is essential for Shiga toxin uptake (16371508) and promotes human rhinovirus internalization in airway epithelial cells via PI3K activation (18178826). Its role also extends to regulating complement-mediated phagocytosis by modulating actin dynamics (16449524), orchestrating platelet activation through GPVI-dependent mechanisms (22489915), supporting selectin-dependent leukocyte rolling (16849645), and mediating IgA immune complex–induced cytokine release in mesangial cells (22956578), while natural compounds such as kaempferol can directly target Syk to downregulate inflammatory gene expression (25922567). Finally, intestinal epithelial cells utilize Syk downstream of β-glucan receptors to secrete chemokines (25251945) and studies on polymorphonuclear neutrophils further emphasize its importance in orchestrating early innate responses (17721605)."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn adaptive immune cells and hematologic malignancies, Syk is indispensable for transducing antigen receptor signals that support both tonic and ligand-induced cell survival. Structural and biochemical analyses have revealed that its catalytic domain is uniquely poised for activation even in the absence of phosphorylation (15507431), a feature that underpins its central role in B-cell receptor (BCR) signaling. In diffuse large B-cell lymphoma and chronic lymphocytic leukemia, Syk-dependent tonic BCR signaling is critical for tumor cell survival, with pharmacological inhibition inducing apoptosis (18006696, 19092849, 19549911, 23764004). Moreover, Syk is co-opted in other lymphoid malignancies—whether activated by constitutive phosphorylation from fusion events in peripheral T-cell lymphoma (20439541), by cooperative interactions with mutant FLT3 in acute myeloid leukemia (24525236), or by transforming pre–B cells through sustained overactivity (17130299)—and contributes to chemotherapy resistance by engaging in networks that include STAT3 phosphorylation under oxidative stress (20133729) and altered TCR signaling via substitution of the TCR ζ-chain (19018007). In chronic myeloid leukemia, aberrant Syk activity cooperating with Lyn kinase further promotes resistance to targeted inhibitors (21730355), and upregulation of Syk has been implicated in Meis1-driven leukemogenesis (28399410)."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "27"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn contrast to its oncogenic functions in hematologic malignancies, Syk displays tumor-suppressive properties in several epithelial cancers. In breast cancer, full-length Syk containing a critical nuclear localization signal suppresses cell invasion and metastasis, whereas an alternatively spliced variant lacking this signal is frequently expressed in tumors and is associated with increased metastatic potential (12445683, 12477728, 12907655). These context-dependent functions underscore Syk’s duality: it acts as a fundamental transducer of immune receptor signaling to promote survival in lymphoid cells while concurrently restraining cell motility and invasion in certain solid tumors."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "28", "end_ref": "30"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ana Urzainqui, Juan M Serrador, Fernando Viedma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ITAM-based interaction of ERM proteins with Syk mediates signaling by the leukocyte adhesion receptor PSGL-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Immunity (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s1074-7613(02)00420-x"}], "href": "https://doi.org/10.1016/s1074-7613(02"}, {"type": "t", "text": "00420-x) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12387735"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12387735"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yasunari Takada, Asok Mukhopadhyay, Gopal C Kundu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hydrogen peroxide activates NF-kappa B through tyrosine phosphorylation of I kappa B alpha and serine phosphorylation of p65: evidence for the involvement of I kappa B alpha kinase and Syk protein-tyrosine kinase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M212389200"}], "href": "https://doi.org/10.1074/jbc.M212389200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12711606"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12711606"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Patrick G Arndt, Naohito Suzuki, Natalie J Avdi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lipopolysaccharide-induced c-Jun NH2-terminal kinase activation in human neutrophils: role of phosphatidylinositol 3-Kinase and Syk-mediated pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M309901200"}], "href": "https://doi.org/10.1074/jbc.M309901200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14699155"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14699155"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "David M Underhill, Eddie Rossnagle, Clifford A Lowell, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dectin-1 activates Syk tyrosine kinase in a dynamic subset of macrophages for reactive oxygen production."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2005-03-1239"}], "href": "https://doi.org/10.1182/blood-2005-03-1239"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15956283"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15956283"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Silje Ugland Lauvrak, Sébastien Wälchli, Tore-Geir Iversen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Shiga toxin regulates its entry in a Syk-dependent manner."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.e05-08-0766"}], "href": "https://doi.org/10.1091/mbc.e05-08-0766"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16371508"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16371508"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Yuhong Shi, Yumi Tohyama, Tomomi Kadono, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Protein-tyrosine kinase Syk is required for pathogen engulfment in complement-mediated phagocytosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2005-09-3616"}], "href": "https://doi.org/10.1182/blood-2005-09-3616"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16449524"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16449524"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Claire Abbal, Martine Lambelet, Debora Bertaggia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lipid raft adhesion receptors and Syk regulate selectin-dependent rolling under flow conditions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2006-04-013912"}], "href": "https://doi.org/10.1182/blood-2006-04-013912"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16849645"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16849645"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Jürgen Schymeinsky, Attila Mócsai, Barbara Walzog "}, {"type": "b", "children": [{"type": "t", "text": "Neutrophil activation via beta2 integrins (CD11/CD18): molecular mechanisms and clinical implications."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Thromb Haemost (2007)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17721605"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17721605"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Christine Lau, Xiaomin Wang, Lihua Song, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Syk associates with clathrin and mediates phosphatidylinositol 3-kinase activation during human rhinovirus internalization."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.180.2.870"}], "href": "https://doi.org/10.4049/jimmunol.180.2.870"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18178826"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18178826"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Sonja I Gringhuis, Jeroen den Dunnen, Manja Litjens, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dectin-1 directs T helper cell differentiation by controlling noncanonical NF-kappaB activation through Raf-1 and Syk."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Immunol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ni.1692"}], "href": "https://doi.org/10.1038/ni.1692"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19122653"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19122653"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Najwane Saïd-Sadier, Eduardo Padilla, Gordon Langsley, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Aspergillus fumigatus stimulates the NLRP3 inflammasome through a pathway requiring ROS production and the Syk tyrosine kinase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0010008"}], "href": "https://doi.org/10.1371/journal.pone.0010008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20368800"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20368800"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "J F Arthur, J Qiao, Y Shen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ITAM receptor-mediated generation of reactive oxygen species in human platelets occurs via Syk-dependent and Syk-independent pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Thromb Haemost (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1538-7836.2012.04734.x"}], "href": "https://doi.org/10.1111/j.1538-7836.2012.04734.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22489915"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22489915"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Min Jeong Kim, John P McDaid, Stephen P McAdoo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Spleen tyrosine kinase is important in the production of proinflammatory cytokines and cell proliferation in human mesangial cells following stimulation with IgA1 isolated from IgA nephropathy patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1102603"}], "href": "https://doi.org/10.4049/jimmunol.1102603"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22956578"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22956578"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Sarit Cohen-Kedar, Liran Baram, Hofit Elad, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human intestinal epithelial cells respond to β-glucans via Dectin-1 and Syk."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Immunol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/eji.201444876"}], "href": "https://doi.org/10.1002/eji.201444876"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25251945"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25251945"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Shi Hyoung Kim, Jae Gwang Park, Jongsung Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The dietary flavonoid Kaempferol mediates anti-inflammatory responses via the Src, Syk, IRAK1, and IRAK4 molecular targets."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mediators Inflamm (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1155/2015/904142"}], "href": "https://doi.org/10.1155/2015/904142"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25922567"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25922567"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Shane Atwell, Jason M Adams, John Badger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel mode of Gleevec binding is revealed by the structure of spleen tyrosine kinase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M409792200"}], "href": "https://doi.org/10.1074/jbc.M409792200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15507431"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15507431"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Thomas Wossning, Sebastian Herzog, Fabian Köhler, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Deregulated Syk inhibits differentiation and induces growth factor-independent proliferation of pre-B cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20060967"}], "href": "https://doi.org/10.1084/jem.20060967"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17130299"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17130299"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Linfeng Chen, Stefano Monti, Przemyslaw Juszczynski, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SYK-dependent tonic B-cell receptor signaling is a rational treatment target in diffuse large B-cell lymphoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2007-07-100115"}], "href": "https://doi.org/10.1182/blood-2007-07-100115"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18006696"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18006696"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Sandeep Krishnan, Yuang-Taung Juang, Bhabadeb Chowdhury, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Differential expression and molecular associations of Syk in systemic lupus erythematosus T cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.181.11.8145"}], "href": "https://doi.org/10.4049/jimmunol.181.11.8145"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19018007"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19018007"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "S Gobessi, L Laurenti, P G Longo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of constitutive and BCR-induced Syk activation downregulates Mcl-1 and induces apoptosis in chronic lymphocytic leukemia B cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Leukemia (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/leu.2008.346"}], "href": "https://doi.org/10.1038/leu.2008.346"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19092849"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19092849"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Maike Buchner, Simon Fuchs, Gabriele Prinz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Spleen tyrosine kinase is overexpressed and represents a potential therapeutic target in chronic lymphocytic leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-08-4252"}], "href": "https://doi.org/10.1158/0008-5472.CAN-08-4252"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19549911"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19549911"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Fatih M Uckun, Sanjive Qazi, Hong Ma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "STAT3 is a substrate of SYK tyrosine kinase in B-lineage leukemia/lymphoma cells exposed to oxidative stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0909086107"}], "href": "https://doi.org/10.1073/pnas.0909086107"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20133729"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20133729"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Konstanze Pechloff, Julian Holch, Uta Ferch, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The fusion kinase ITK-SYK mimics a T cell receptor signal and drives oncogenesis in conditional mouse models of peripheral T cell lymphoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20092042"}], "href": "https://doi.org/10.1084/jem.20092042"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20439541"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20439541"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Romain Gioia, Cédric Leroy, Claire Drullion, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Quantitative phosphoproteomics revealed interplay between Syk and Lyn in the resistance to nilotinib in chronic myeloid leukemia cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2010-10-313692"}], "href": "https://doi.org/10.1182/blood-2010-10-313692"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21730355"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21730355"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Linfeng Chen, Stefano Monti, Przemyslaw Juszczynski, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SYK inhibition modulates distinct PI3K/AKT- dependent survival pathways and cholesterol biosynthesis in diffuse large B cell lymphomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cell (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ccr.2013.05.002"}], "href": "https://doi.org/10.1016/j.ccr.2013.05.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23764004"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23764004"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Alexandre Puissant, Nina Fenouille, Gabriela Alexe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SYK is a critical regulator of FLT3 in acute myeloid leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cell (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ccr.2014.01.022"}], "href": "https://doi.org/10.1016/j.ccr.2014.01.022"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24525236"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24525236"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Sebastian Mohr, Carmen Doebele, Federico Comoglio, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hoxa9 and Meis1 Cooperatively Induce Addiction to Syk Signaling by Suppressing miR-146a in Acute Myeloid Leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cell (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ccell.2017.03.001"}], "href": "https://doi.org/10.1016/j.ccell.2017.03.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28399410"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28399410"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Tatsuya Toyama, Hirotaka Iwase, Hiroko Yamashita, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Reduced expression of the Syk gene is correlated with poor prognosis in human breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0304-3835(02)00463-9"}], "href": "https://doi.org/10.1016/s0304-3835(02"}, {"type": "t", "text": "00463-9) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12445683"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12445683"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Ganapati H Mahabeleshwar, Gopal C Kundu "}, {"type": "b", "children": [{"type": "t", "text": "Syk, a protein-tyrosine kinase, suppresses the cell motility and nuclear factor kappa B-mediated secretion of urokinase type plasminogen activator by inhibiting the phosphatidylinositol 3'-kinase activity in breast cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M208905200"}], "href": "https://doi.org/10.1074/jbc.M208905200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12477728"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12477728"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Lei Wang, Lindsay Duke, Peter S Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Alternative splicing disrupts a nuclear localization signal in spleen tyrosine kinase that is required for invasion suppression in breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2003)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12907655"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12907655"}]}]}]}