syk kinase


Summary: An SH2 domain-containing non-receptor tyrosine kinase that regulates signal transduction downstream of a variety of receptors including B-CELL ANTIGEN RECEPTORS. It functions in both INNATE IMMUNITY and ADAPTIVE IMMUNITY and also mediates signaling in CELL ADHESION; OSTEOGENESIS; PLATELET ACTIVATION; and vascular development.

Top Publications

  1. Lima Júnior D, Mineo T, Calich V, Zamboni D. Dectin-1 Activation during Leishmania amazonensis Phagocytosis Prompts Syk-Dependent Reactive Oxygen Species Production To Trigger Inflammasome Assembly and Restriction of Parasite Replication. J Immunol. 2017;199:2055-2068 pubmed publisher
    ..amazonensis phagocytosis is important for macrophage restriction of the parasite replication and effectively accounts for host resistance to Leishmania infection. ..
  2. Gurung P, Fan G, Lukens J, Vogel P, Tonks N, Kanneganti T. Tyrosine Kinase SYK Licenses MyD88 Adaptor Protein to Instigate IL-1?-Mediated Inflammatory Disease. Immunity. 2017;46:635-648 pubmed publisher
    ..Overall, these studies identify SHP1 and SYK crosstalk as a critical regulator of MyD88 post-translational modifications and IL-1-driven inflammation. ..
  3. Yang W, Nam G, Kim M, Cho J. Syk-Mediated Suppression of Inflammatory Responses by Cordyceps bassiana. Am J Chin Med. 2017;45:1217-1232 pubmed publisher
    ..These results strongly suggest that Cm-WE suppresses inflammatory responses by inhibiting Syk kinase activity, with potential implications for novel neutraceutic and pharmaceutic biomaterials.
  4. Nemeth T, Virtic O, Sitaru C, Mocsai A. The Syk Tyrosine Kinase Is Required for Skin Inflammation in an In Vivo Mouse Model of Epidermolysis Bullosa Acquisita. J Invest Dermatol. 2017;137:2131-2139 pubmed publisher
  5. Daley D, Mani V, Mohan N, Akkad N, Ochi A, Heindel D, et al. Dectin 1 activation on macrophages by galectin 9 promotes pancreatic carcinoma and peritumoral immune tolerance. Nat Med. 2017;23:556-567 pubmed publisher
    ..These data suggest that targeting dectin 1 signaling is an attractive strategy for developing an immunotherapy for PDA. ..
  6. Udyavar A, Hoeksema M, Clark J, Zou Y, Tang Z, Li Z, et al. Co-expression network analysis identifies Spleen Tyrosine Kinase (SYK) as a candidate oncogenic driver in a subset of small-cell lung cancer. BMC Syst Biol. 2013;7 Suppl 5:S1 pubmed publisher
    ..This strategy is especially useful in cancer types where no actionable mutations have emerged. ..
  7. Rychter J, Clave P. Intestinal inflammation in postoperative ileus: pathogenesis and therapeutic targets. Gut. 2013;62:1534-5 pubmed publisher
  8. Philippen A, Diener S, Zenz T, Dohner H, Stilgenbauer S, Mertens D. SYK carries no activating point mutations in patients with chronic lymphocytic leukaemia (CLL). Br J Haematol. 2010;150:633-6 pubmed publisher
  9. Uckun F, Myers D, Cheng J, Qazi S. Liposomal Nanoparticles of a Spleen Tyrosine Kinase P-Site Inhibitor Amplify the Potency of Low Dose Total Body Irradiation Against Aggressive B-Precursor Leukemia and Yield Superior Survival Outcomes in Mice. EBioMedicine. 2015;2:554-62 pubmed publisher

More Information


  1. Nam S, Park Y, Kim H, Kim H, Lee D, Lee M, et al. Suppression of IgE-mediated mast cell activation and mouse anaphylaxis via inhibition of Syk activation by 8-formyl-7-hydroxy-4-methylcoumarin, 4?8C. Toxicol Appl Pharmacol. 2017;332:25-31 pubmed publisher
    ..This suggests that 4?8C can be used as a new medicinal candidate to control allergic diseases such as seasonal allergies and atopic dermatitis. ..
  2. Redhu N, Saleh A, Lee H, Halayko A, Ziegler S, Gounni A. IgE induces transcriptional regulation of thymic stromal lymphopoietin in human airway smooth muscle cells. J Allergy Clin Immunol. 2011;128:892-896.e2 pubmed publisher
  3. Ramessur Chandran S, Han Y, Tesch G, Di Paolo J, Mulley W, Kanellis J, et al. Inhibition of Spleen Tyrosine Kinase Reduces Renal Allograft Injury in a Rat Model of Acute Antibody-Mediated Rejection in Sensitized Recipients. Transplantation. 2017;101:e240-e248 pubmed publisher
    ..Further studies are warranted to determine whether Syk inhibition is a potential adjunctive treatment in clinical AMR. ..
  4. Weis V, Königsberger S, Amler S, Wienands J, Kiefer F. Unperturbed Immune Function despite Mutation of C-Terminal Tyrosines in Syk Previously Implicated in Signaling and Activity Regulation. Mol Cell Biol. 2017;37: pubmed publisher
  5. Corr E, Cunningham C, Helbert L, McCarthy G, Dunne A. Osteoarthritis-associated basic calcium phosphate crystals activate membrane proximal kinases in human innate immune cells. Arthritis Res Ther. 2017;19:23 pubmed publisher
  6. Furukawa K, Fuse I, Iwakura Y, Sotoyama H, Hanyu O, Nawa H, et al. Advanced glycation end products induce brain-derived neurotrophic factor release from human platelets through the Src-family kinase activation. Cardiovasc Diabetol. 2017;16:20 pubmed publisher
    ..Chronic elevation of AGEs may induce depletion or downregulation of BDNF in platelets during the progression of DM. ..
  7. Yin G, Yang X, Li Q, Guo Z. SYK protects cardiocytes against anoxia and hypoglycemia-induced injury in ischemic heart failure. Mol Immunol. 2017;91:35-41 pubmed publisher
    ..Furthermore, we observed that SYK could induce HO-1 expression by regulating the Akt phosphorylation level in H9c2 with A/H injury, protecting H9c2 from the injury induced by A/H treatment. ..
  8. Coebergh van den Braak R, Sieuwerts A, Kandimalla R, Lalmahomed Z, Bril S, van Galen A, et al. High mRNA expression of splice variant SYK short correlates with hepatic disease progression in chemonaive lymph node negative colon cancer patients. PLoS ONE. 2017;12:e0185607 pubmed publisher
    ..This association could however not be confirmed in two independent smaller cohorts, suggesting that further extensive validation is needed to confirm the prognostic value of SYK(S) expression in chemonaive LNN colon cancer. ..
  9. Badolia R, Inamdar V, Manne B, Dangelmaier C, Eble J, Kunapuli S. Gq pathway regulates proximal C-type lectin-like receptor-2 (CLEC-2) signaling in platelets. J Biol Chem. 2017;292:14516-14531 pubmed publisher
    ..Together, these results provide evidence for novel Gq-PLC?-PKC?-mediated regulation of proximal CLEC-2 signaling by Gq-coupled receptors. ..
  10. Yaktapour N, Meiss F, Mastroianni J, Zenz T, Andrlova H, Mathew N, et al. BRAF inhibitor-associated ERK activation drives development of chronic lymphocytic leukemia. J Clin Invest. 2014;124:5074-84 pubmed publisher
    ..Together, these results suggest that BRAF inhibitors promote B cell malignancies in the absence of obvious mutations in RAS or other receptor tyrosine kinases and provide a rationale for combined BRAF/MEK or BRAF/SYK inhibition. ..
  11. Lopez Guerra M, Xargay Torrent S, Perez Galan P, Saborit Villarroya I, Rosich L, Villamor N, et al. Sorafenib targets BCR kinases and blocks migratory and microenvironmental survival signals in CLL cells. Leukemia. 2012;26:1429-32 pubmed publisher
  12. Pantaleo A, Kesely K, Pau M, Tsamesidis I, Schwarzer E, Skorokhod O, et al. Syk inhibitors interfere with erythrocyte membrane modification during P falciparum growth and suppress parasite egress. Blood. 2017;130:1031-1040 pubmed publisher
    ..We demonstrate here that multiple Syk kinase inhibitors both prevent parasite-induced band 3 tyrosine phosphorylation and inhibit parasite-promoted membrane ..
  13. Varnum M, Clayton K, Yoshii Kitahara A, Yonemoto G, Koro L, Ikezu S, et al. A split-luciferase complementation, real-time reporting assay enables monitoring of the disease-associated transmembrane protein TREM2 in live cells. J Biol Chem. 2017;292:10651-10663 pubmed publisher
    ..These results demonstrate that our TREM2 reporter vector is a novel tool for monitoring the TREM2-TYROBP interaction in real time. ..
  14. Botschuijver S, Roeselers G, Levin E, Jonkers D, Welting O, Heinsbroek S, et al. Intestinal Fungal Dysbiosis Is Associated With Visceral Hypersensitivity in Patients With Irritable Bowel Syndrome and Rats. Gastroenterology. 2017;153:1026-1039 pubmed publisher
    ..The intestinal fungi might therefore be manipulated for treatment of IBS-related visceral hypersensitivity. ..
  15. McDonald D, Brunden K, Landreth G. Amyloid fibrils activate tyrosine kinase-dependent signaling and superoxide production in microglia. J Neurosci. 1997;17:2284-94 pubmed
  16. Hess P, Rawnsley D, Jakus Z, Yang Y, Sweet D, Fu J, et al. Platelets mediate lymphovenous hemostasis to maintain blood-lymphatic separation throughout life. J Clin Invest. 2014;124:273-84 pubmed
    ..Collectively, these studies unveil a newly recognized form of hemostasis that functions with the LVV to safeguard the lymphatic vascular network throughout life. ..
  17. Liao C, Hsu J, Kim Y, Hu D, Xu D, Zhang J, et al. Selective inhibition of spleen tyrosine kinase (SYK) with a novel orally bioavailable small molecule inhibitor, RO9021, impinges on various innate and adaptive immune responses: implications for SYK inhibitors in autoimmune disease therapy. Arthritis Res Ther. 2013;15:R146 pubmed publisher
    ..Inhibition of SYK kinase activity impinges on various innate and adaptive immune responses...
  18. Liang Y, Song D, Liang S, Zhang Z, Gao L, Fan X. The hemagglutinin-neuramidinase protein of Newcastle disease virus upregulates expression of the TRAIL gene in murine natural killer cells through the activation of Syk and NF-?B. PLoS ONE. 2017;12:e0178746 pubmed publisher
    ..We concluded that killer activation receptors pathway is involved in the IFN-?-independent TRAIL expression of NDV-stimulated NK cells, and these are activated by Syk and NF-?B. ..
  19. Kitai M, Fukuda N, Ueno T, Endo M, Maruyama T, Abe M, et al. Effects of a spleen tyrosine kinase inhibitor on progression of the lupus nephritis in mice. J Pharmacol Sci. 2017;134:29-36 pubmed publisher
  20. Killpack T, Ballesteros M, Bunnell S, Bedugnis A, Kobzik L, Hu L, et al. Phagocytic Receptors Activate Syk and Src Signaling during Borrelia burgdorferi Phagocytosis. Infect Immun. 2017;85: pubmed publisher
    ..Thus, we report that multiple pathways participate in B. burgdorferi internalization and that different cell surface receptors act simultaneously in cooperation and independently to mediate phagocytosis. ..
  21. Matsumaru T, Inai M, Ishigami K, Iwamatsu T, Maita H, Otsuguro S, et al. Divergent synthesis of kinase inhibitor derivatives, leading to discovery of selective Gck inhibitors. Bioorg Med Chem Lett. 2017;27:2144-2147 pubmed publisher
    ..Spleen tyrosine kinase (Syk) and germinal center kinase (Gck, MAP4K2) inhibition assays showed that some of the synthesized compounds were selective Gck inhibitors. ..
  22. Marczynke M, Gröger K, Seitz O. Selective Binders of the Tandem Src Homology 2 Domains in Syk and Zap70 Protein Kinases by DNA-Programmed Spatial Screening. Bioconjug Chem. 2017;28:2384-2392 pubmed publisher
    ..The spatial screen led to the design of mutually selective, DNA-free binders, which discriminate Zap-70 and Syk tSH2 by 1 order of magnitude in affinity. ..
  23. Lou Z, Jevremovic D, Billadeau D, Leibson P. A balance between positive and negative signals in cytotoxic lymphocytes regulates the polarization of lipid rafts during the development of cell-mediated killing. J Exp Med. 2000;191:347-54 pubmed
    ..These results suggest that the influence of integrated positive and negative signals on raft redistribution critically influences the development of cell-mediated cytotoxicity. ..
  24. Keller B, Stumpf I, Strohmeier V, Usadel S, Verhoeyen E, Eibel H, et al. High SYK Expression Drives Constitutive Activation of CD21low B Cells. J Immunol. 2017;198:4285-4292 pubmed publisher
  25. Wang Y, Jiang L, Mo X, Lan Y, Yang X, Liu X, et al. Megakaryocytic Smad4 Regulates Platelet Function through Syk and ROCK2 Expression. Mol Pharmacol. 2017;92:285-296 pubmed publisher
    ..These results suggest potential links among Smad4 deficiency, attenuated Syk, and ROCK2 expression and defective platelet activation. ..
  26. Combs C, Johnson D, Cannady S, Lehman T, Landreth G. Identification of microglial signal transduction pathways mediating a neurotoxic response to amyloidogenic fragments of beta-amyloid and prion proteins. J Neurosci. 1999;19:928-39 pubmed
    ..This toxicity can be ameliorated by treating THP-1 cells with specific enzyme inhibitors that target various components of the signal transduction pathway linked to the inflammatory responses. ..