Syk Expression and Novel Function in a Wide Variety of Tissues

doi:10.1006/bbrc.2001.5788

Biochemical and Biophysical Research Communications

Volume 288, Issue 3, 2 November 2001, Pages 495-498

https://doi.org/10.1006/bbrc.2001.5788 Get rights and content

Abstract

Syk protein-tyrosine kinase has been implicated in a variety of hematopoietic cell responses, in particular immunoreceptor signaling events that mediate diverse cellular responses including proliferation, differentiation, and phagocytosis. On the other hand, Syk exhibits a more widespread expression pattern in nonhematopoietic cells like fibroblasts, epithelial cells, breast tissue, hepatocytes, neuronal cells, and vascular endothelial cells and has been shown to be functionally important on these cell types. Thus, Syk appears to play a general physiological function in a wide variety of cells. In this article, we briefly review the current literature regarding the expression and novel function of Syk in various cells and tissues.

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Cited by (155)

Spleen tyrosine kinase (SYK) signals are implicated in cardio-cerebrovascular diseases
2023, Heliyon
Post-translational modifications regulate numerous biochemical reactions and functions through covalent attachment to proteins. Phosphorylation, acetylation and ubiquitination account for over 90% of all reported post-translational modifications. As one of the tyrosine protein kinases, spleen tyrosine kinase (SYK) plays crucial roles in many pathophysiological processes and affects the pathogenesis and progression of various diseases. SYK is expressed in tissues outside the hematopoietic system, especially the heart, and is involved in the progression of various cardio-cerebrovascular diseases, such as atherosclerosis, heart failure, diabetic cardiomyopathy, stroke and others. Knowledge on the role of SYK in the progress of cardio-cerebrovascular diseases is accumulating, and many related mechanisms have been discovered and validated. This review summarizes the role of SYK in the progression of various cardio-cerebrovascular diseases, and aims to provide a theoretical basis for future experimental and clinical research targeting SYK as a therapeutic option for these diseases.
Immunoregulatory mechanism of acute kidney injury in sepsis: A Narrative Review
2023, Biomedicine and Pharmacotherapy
Sepsis acute kidney injury (SAKI) is a common complication of sepsis, accounting for 26–50 % of all acute kidney injury (AKI). AKI is an independent risk factor for increased mortality risk in patients with sepsis. The excessive inflammatory cascade reaction in SAKI is one of the main causes of kidney damage. Both the innate immune system and the adaptive immune system are involved in the inflammation process of SAKI. Under the action of endotoxin, neutrophils, monocytes, macrophages, T cells and other complex immune network reactions occur, and a large number of endogenous inflammatory mediators are released, resulting in the amplification and loss of control of the inflammatory response. The study of immune cells in SAKI will help improve the understanding of the immune mechanisms of SAKI, and will lay a foundation for the development of new diagnostic and therapeutic targets. This article reviews the role of known immune mechanisms in the occurrence and development of SAKI, with a view to finding new targets for SAKI treatment.
The role of Syk phosphorylation in Fc receptor mediated mIgM<sup>+</sup> B lymphocyte phagocytosis in flounder (Paralichthys olivaceus)
2022, Fish and Shellfish Immunology
Spleen tyrosine kinase (Syk) is a non-receptor protein tyrosine kinase, and it mediates downstream signaling of FcR-mediated immune responses. Our previous work revealed that the expression of Syk was significantly up-regulated in flounder mIgM⁺ B lymphocytes after phagocytosis of antiserum-opsonized Edwardsiella tarda, which suggested Syk might be involved in Ig-opsonized phagocytosis. In this paper, phospho-Syk (pSyk) inhibitor was used to investigate the potential role of phosphorylated Syk in FcR-mediated phagocytosis of IgM⁺ B cells. Indirect immunofluorescence assay (IFA) and Western blotting showed that the level of phosphorylated Syk in the mIgM⁺ B lymphocytes treated with pSyk inhibitor was significantly lower compared to the control group after stimulation with flounder antiserum. Flow cytometry analysis showed that after 3 h incubation with antiserum-opsonized E. tarda, the phagocytosis rates of mIgM⁺ B lymphocytes from peripheral blood, spleen and head kidney pre-treated with pSyk inhibitor were 48.1%, 40.1% and 43.6% respectively, which were significantly lower than that of the control groups with 58.7%, 53.2% and 57.4%, respectively. And likewise, after pSyk inhibitor treatment, the proportions of mIgM⁺ B lymphocytes with higher intracellular reactive oxygen species (ROS) levels in peripheral blood, spleen and head kidney decreased to 15.2%, 12.0% and 12.1% from the control level of 26.5%, 25.9% and 26.3%, respectively. Moreover, the expression of three genes affected by pSyk, including phospholipase Cγ1 (PLCγ1), phospholipase Cγ2 (PLCγ2) and phosphatidylinositol 3 kinase (PI3K) were found to be significantly down-regulated in pSyk inhibitor-treated mIgM⁺ B lymphocytes post phagocytosis. These results suggest that pSyk plays a key role in FcR-mediated phagocytosis and bactericidal activity of mIgM⁺ B lymphocytes, which promotes further understanding of the regulatory role of pSyk in teleost B cells phagocytosis.
Small-molecule screening identifies Syk kinase inhibition and rutaecarpine as modulators of macrophage training and SARS-CoV-2 infection
2022, Cell Reports
Biologically active small molecules can impart modulatory effects, in some cases providing extended long-term memory. In a screen of biologically active small molecules for regulators of tumor necrosis factor (TNF) induction, we identify several compounds with the ability to induce training effects on human macrophages. Rutaecarpine shows acute and long-term modulation, enhancing lipopolysaccharide (LPS)-induced pro-inflammatory cytokine secretion and relieving LPS tolerance in human macrophages. Rutaecarpine inhibits β-glucan-induced H3K4Me3 marks at the promoters of several pro-inflammatory cytokines, highlighting the potential of this molecule to modulate chromosomal topology. Syk kinase inhibitor (SYKi IV), another screen hit, promotes an enhanced response to LPS similar to that previously reported for β-glucan-induced training. Macrophages trained with SYKi IV show a high degree of resistance to influenza A, multiple variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and OC43 coronavirus infection, highlighting a potential application of this molecule and other SYKis as prophylactic treatments for viral susceptibility.
Molecular and immunomodulatory actions of new antiasthmatic agents: Exploring the diversity of biologics in Th2 endotype asthma
2022, Pharmacological Research
Citation Excerpt :
Syk is one of the principal regulators of intracellular signalling pathway involved in inflammatory response, mast cell activation, macrophages, and participates routinely in cytokine signalling [208]. It is predominantly expressed in hematopoietic tissues as well as in a variety of non-hematopoietic tissues including respiratory epithelial cells [209,210]. This tyrosine kinase is involved in propagating signal transduction in a variety of immunoreceptors tyrosine-based activation motif (ITAM) dependent proinflammatory cascade involving integrin signalling Fc receptor, B cells receptor (BCR), T cell receptor (TCR); collectively known as classical immunoreceptors [211].
Asthma is a major respiratory disorder characterised by chronic inflammation and airway remodelling. It affects about 1–8% of the global population and is responsible for over 461,000 deaths annually. Until recently, the pharmacotherapy of severe asthma involved high doses of inhaled corticosteroids in combination with β-agonist for prolonged action, including theophylline, leukotriene antagonist or anticholinergic yielding limited benefit. Although the use of newer agents to target Th2 asthma endotypes has improved therapeutic outcomes in severe asthmatic conditions, there seems to be a paucity of understanding the diverse mechanisms through which these classes of drugs act. This article delineates the molecular and immunomodulatory mechanisms of action of new antiasthmatic agents currently being trialled in preclinical and clinical studies to remit asthmatic conditions. The ultimate goal in developing antiasthmatic agents is based on two types of approaches: either anti-inflammatory or bronchodilators. Biologic and most small molecules have been shown to modulate specific asthma endotypes, targeting thymic stromal lymphopoietin, tryptase, spleen tyrosine kinase (Syk), Janus kinase, PD-L1/PD-L2, GATA-3, and CD38 for the treatment and management of Th2 endotype asthma.
Spleen tyrosine kinase regulates keratinocyte inflammasome activation and skin inflammation induced by UVB irradiation
2022, Free Radical Biology and Medicine
Citation Excerpt :
These results indicate that the Syk inhibitor R406 exerts a protective role in UVB-induced skin barrier damage and inflammation. Although Syk is expressed by different nonhematopoietic cells, including skin keratinocytes [6,8,11], its functions in the skin tissue were still elusive. A previous report demonstrating the inhibition of UVB-induced matrix metalloproteinase-1 expression in the presence of a Syk inhibitor or following Syk knockdown in human skin dermal fibroblasts suggests a role of Syk in UV-mediated skin damage [21].
UVB can induce inflammatory responses contributing to diverse skin damage. UVB-triggered inflammasome activation of human keratinocytes underlies UVB-induced skin sunburn reaction. Pleiotropic functions of spleen tyrosine kinase (Syk) have rendered it as a potential therapeutic target. In immunocytes, Syk modulates immunoreceptor signaling and NLRP3 inflammasome activation. In skin, Syk mediates EGFR signaling, regulates keratinocyte differentiation and is involved in inflammatory disorders. However, roles of Syk in UVB-induced inflammasome activation in keratinocytes remain elusive. We investigated roles of keratinocyte Syk in UVB-triggered photo-responses. Primary normal human epidermal keratinocytes (NHEKs) isolated from skin were used. Syk knockdown or Syk inhibitor R406 was applied to investigate functions of keratinocyte Syk in UVB photobiology. The possible in vivo role of Syk was evaluated by checking UVB-induced skin damage in R406-treated mice. UVB was able to induce Syk phosphorylation in NHEKs that could be regulated by reactive oxygen species (ROS) generation and EGFR. Syk knockdown or Syk inhibitor (R406) treatment reduced UVB-triggered apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) crosslinking, procaspase-1 cleavage, active IL-1β formation, and gasdermin D activation, indicating roles of Syk in UVB-triggered inﬂammasome activation in keratinocytes. UVB-induced production of IL-8, TNF-α, ROS, and phosphorylation of JNK and p38 were attenuated after Syk knockdown or inhibition. R406 ameliorated UVB-induced mouse skin damage, including erythema and transepidermal water loss (TEWL). Thus, Syk participated in UVB-induced inflammasome activation and inflammatory response in vitro and in vivo, suggesting potential photo-protective effects of Syk inhibition in UVB-induced skin inflammation.

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¹: To whom correspondence should be addressed. Fax: 81-78-382-5419. E-mail: [email protected].

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Breakthroughs & ViewsSyk Expression and Novel Function in a Wide Variety of Tissues

Abstract

J. Biol. Chem.

Cell. Signal.

Blood

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

Biochem. Biophys. Res. Commun.

FEBS Lett.

Blood

Biochem. Biophys. Res. Commun.

Genetic analysis of B cell antigen receptor signaling

Annu. Rev. Immunol.

Tyrosine kinase SYK: Essential functions for immunoreceptor signalling

Immunol. Today

Breakthroughs & Views
Syk Expression and Novel Function in a Wide Variety of Tissues