scholarly journals Inhibitory Effects of Eriodictyol-7-O-β-d-glucuronide and 5,7-Dihydroxy-4-chromene Isolated from Chrysanthemum zawadskii var. latilobum in FcεRI-Mediated Human Basophilic KU812F Cell Activation

Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 994 ◽  
Author(s):  
Mina Lee ◽  
Sun-Yup Shim
Keyword(s):  
Cell Surface ◽  
Common Cold ◽  
Tyrosine Kinases ◽  
Messenger Rna ◽  
Cell Activation ◽  
Protein Tyrosine Kinases ◽  
Inhibitory Effects ◽  
The Common ◽  
Allergic Disorders ◽  
Chrysanthemum Zawadskii

Chrysanthemum zawadskii var. latilobum (CZL) has been used in Eastern medicine for the treatment of various diseases, such as pneumonia, bronchitis, cough, the common cold, pharyngitis, bladder-related disorders, gastroenteric disorders, and hypertension. In the present study, we isolated two strong antiallergic compounds from CZL, namely, eriodictyol-7-O-β-d-glucuronide (EDG) and 5,7-dihydroxy-4-chromene (DC), and investigated their antiallergic effects in FcεRI-mediated human basophilic KU812F cells. EDG and DC downregulated the protein and messenger RNA (mRNA) expression of FcεRI on the cell surface. Moreover, Western blotting analysis showed that EDG and DC inhibited the expression of protein tyrosine kinases such as Syk and Lyn, and extracellular-regulated kinases (ERK) 1/2. These results suggested that EDG and DC, antiallergic constituents of CZL, are potential therapeutic candidates for protection against and for the treatment of allergic disorders.

GPI-anchored cell-surface molecules complexed to protein tyrosine kinases

Science ◽  
1991 ◽  
Vol 254 (5034) ◽  
pp. 1016-1019 ◽  
Author(s):  
I Stefanova ◽  
V Horejsi ◽  
I. Ansotegui ◽  
W Knapp ◽  
H Stockinger
Keyword(s):  
Cell Surface ◽  
Tyrosine Kinases ◽  
Protein Tyrosine Kinases ◽  
Cell Surface Molecules ◽  
Protein Tyrosine ◽  
Surface Molecules

scholarly journals Recombinant glycosyl-phosphatidylinositol-anchored proteins are not associated with protein kinases in transfected thymoma cells

1994 ◽  
Vol 304 (3) ◽  
pp. 853-859 ◽  
Author(s):  
P M Clissold
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Tyrosine Kinases ◽  
Cell Activation ◽  
Signal Sequence ◽  
Phosphatidyl Inositol ◽  
Protein Tyrosine Kinases ◽  
Receptor Protein ◽  
Protein Tyrosine ◽  
Stable Transfectants

The cross-linking by antibody of some glycosyl-phosphatidyl-inositol (GPI)-anchored proteins on the plasma membrane of T cells leads to cell activation. Phosphorylation of proteins on tyrosine residues has a central role in the control of T cell activation, and non-receptor protein tyrosine kinases can be coprecipitated with immune complexes of GPI-anchored proteins in T cell lysates. In order to investigate the nature of this interaction, two recombinant GPI-anchored proteins were constructed (using the GPI signal sequence from Thy-1), and their associations with protein tyrosine kinases in stable transfectants of a mouse thymoma have been investigated. One recombinant GPI protein is the extracellular domain of the human complement receptor-1, normally an integral membrane protein, and the other is the secreted protein, human tissue inhibitor of metalloproteinases. The latter protein should be foreign to the cell surface and yet has been expressed as a GPI-anchored protein at levels equivalent to the highly expressed antigens Thy-1 and Ly6.A2 on mouse thymoma cells. Neither of the two recombinant proteins, when immunoprecipitated from NP40 lysates of transfected cells, was associated with protein tyrosine kinases in contrast with the natural endogenous GPI-anchored proteins Thy-1 and Ly6.A2 in non-transfected parental cells. Moreover, high expression of foreign recombinant GPI protein appears to interfere with the association of the natural GPI proteins with protein tyrosine kinases.

scholarly journals FAK and PYK2 are specifically associated with the activated phagocytic receptor complexes from human U937 cells.

2021 ◽  
Author(s):  
Marwan G. AbidAlthagafi
Keyword(s):  
Cell Surface ◽  
Tyrosine Kinases ◽  
Laser Scanning ◽  
Surface Proteins ◽  
Protein Tyrosine Kinases ◽  
Macrophage Cell ◽  
Protein Tyrosine ◽  
Surface Receptors ◽  
Receptor Complexes

The innate immune system is the first shield against foreign attack inside the human body, and it is usually carried out with phagocytosis. An essential macrophage cell surface protein is the Fc receptor which contributes to the engulfment of unknown antigens. One of the important members of Fc receptors is the gamma receptor that binds to the immunoglobulin G (IgG) ligand. Another key receptor in this study is the CD36 receptor, which plays a crucial role in the progression of atherosclerosis, the hardening of arteries, with its ligand oxidized low-density lipoprotein (OxLDL). In this report, protein tyrosine kinase enzymes have been detected in the involvement of receptor complexes with human U937 macrophages, specifically PTK2 and PTK2b genes. Protein tyrosine kinases were known to promote cell migration as a main player in intracellular signal transduction cascades in relation to extracellular stimuli. Cell surface proteins are essential for the immunization of various diseases; yet, the molecular machinery of surface receptors remains unclear. This research primarily examined the dynamic nature of protein tyrosine kinases in an ongoing investigation of macrophage cell surface receptors, particularly the role of Fc γ and CD36 receptors with their ligands IgG and oxLDL coated beads in phagocytosis. Our report demonstrates a novel role of PTK2 and PTK2b functions in relation to U937 CD36-mediated phagocytosis. The Phagocytic efficiency of U937 macrophages was analyzed using laser scanning confocal microscope after silencing the cells with siRNA followed by quantitative counting of phagocytosis. The PF drug FAK inhibitor was also introduced to compare the phagocytic efficiency of siRNA cells.

Association of Src-like protein tyrosine kinases with the CD2 cell surface molecule in rat T lymphocytes and natural killer cells

1992 ◽  
Vol 12 (12) ◽  
pp. 5548-5554
Author(s):  
G M Bell ◽  
J B Bolen ◽  
J B Imboden
Keyword(s):  
Natural Killer Cells ◽  
T Lymphocytes ◽  
Cell Surface ◽  
Natural Killer ◽  
Tyrosine Kinases ◽  
Protein Tyrosine Kinases ◽  
Surface Molecule ◽  
Cell Surface Molecule ◽  
Killer Cells ◽  
Protein Tyrosine

The cell surface molecule CD2 has a signaling role in the activation of T lymphocytes and natural killer cells. Because perturbation of CD2 leads to the appearance of tyrosine-phosphorylated proteins, we investigated the possibility that CD2 associates with cytoplasmic protein tyrosine kinases. As determined by in vitro kinase assays and phosphoamino acid analysis, protein tyrosine kinase activity coprecipitated with CD2 from rat T lymphocytes, T lymphoblasts, thymocytes, interleukin-2-activated natural killer cells, and RNK-16 cells (a rat natural killer cell line). In each case, both p56lck and p59fyn were identified in the CD2 immunoprecipitate. In the thymus, the association between CD2 and these kinases occurred predominately in a small subset of thymocytes that had the cell surface phenotype of mature T cells, indicating that the association is a regulated event and occurs late in T-cell ontogeny. The finding that CD2 is associated with p56lck and p59fyn in detergent lysates suggests that interactions with these Src-like protein kinases play a critical role in CD2-mediated signal transduction.

scholarly journals Genetic Evidence of a Role for Lck in T-Cell Receptor Function Independent or Downstream of ZAP-70/Syk Protein Tyrosine Kinases

1998 ◽  
Vol 18 (5) ◽  
pp. 2855-2866 ◽  
Author(s):  
Jane Wong ◽  
David Straus ◽  
Andrew C. Chan
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Tyrosine Kinases ◽  
Cell Activation ◽  
Interleukin 2 ◽  
Protein Tyrosine Kinases ◽  
Homologous Region ◽  
Activation Markers ◽  
Protein Tyrosine ◽  
Signaling Events

ABSTRACT T-cell antigen receptor (TCR) engagement results in sequential activation of the Src protein tyrosine kinases (PTKs) Lck and Fyn and the Syk PTKs, ZAP-70 and Syk. While the Src PTKs mediate the phosphorylation of TCR-associated signaling subunits and the phosphorylation and activation of the Syk PTKs, the lack of a constitutively active Syk PTK has prohibited the analysis of Lck function downstream of these initiating signaling events. We describe here the generation of an activated Syk family PTK by substituting the kinase domain of Syk for the homologous region in ZAP-70 (designated as KS for kinase swap). Expression of the KS chimera resulted in its autophosphorylation, the phosphorylation of cellular proteins, the upregulation of T-cell activation markers, and the induction of interleukin-2 gene synthesis in a TCR-independent fashion. The KS chimera and downstream ZAP-70 or Syk substrates, such as SLP-76, were still phosphorylated when expressed in Lck-deficient JCaM1.6 T cells. However, expression of the KS chimera in JCaM1.6 cells failed to rescue downstream signaling events, demonstrating a functional role for Lck beyond the activation of the ZAP-70 and Syk PTKs. These results indicate that downstream TCR signaling pathways may be differentially regulated by ZAP-70 and Lck PTKs and provide a mechanism by which effector functions may be selectively activated in response to TCR stimulation.

scholarly journals CD28 ligation in T-cell activation: evidence for two signal transduction pathways

Blood ◽  
1990 ◽  
Vol 75 (7) ◽  
pp. 1531-1539 ◽  
Author(s):  
JA Ledbetter ◽  
JB Imboden ◽  
GL Schieven ◽  
LS Grosmaire ◽  
PS Rabinovitch ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Surface ◽  
T Cell Activation ◽  
Messenger Rna ◽  
Protein Tyrosine Kinase ◽  
Cell Activation ◽  
Mrna Stabilization ◽  
Direct Initiation ◽  
Inositol Phospholipid

The CD28 homodimer is thought to function as a signal transducing receptor during activation of T cells. Evidence is presented that the degree of aggregation of CD28 on the cell surface regulates two distinct CD28-associated signals. Binding of bivalent CD28 monoclonal antibody (MoAb) 9.3 upregulates lymphokine production by messenger RNA (mRNA) stabilization, without direct initiation of lymphokine mRNA transcription. This signal was not dependent on inositol phospholipid production or activation of a protein tyrosine kinase (PTK). In contrast, further crosslinking of CD28 on the cell surface rapidly induced formation of large amounts of inositol trisphosphate (InsP3) and increased cytoplasmic calcium concentration [( Ca2+]i), but did not stimulate PTK. CD28 crosslinking directly activated a subset of resting T cells, since CD25 (interleukin [IL]-2 receptor alpha chain) mRNA was rapidly induced in purified T cells, and proliferation, even without addition of exogenous IL-2, was sometimes observed. CD25 expression was detected on the cell surface of approximately 20% of CD4+ T cells. The degree of CD28 aggregation required for activation was investigated by preparing soluble 9.3 x 9.3 conjugates ranging in size from approximately 300 Kd to greater than 1,000 Kd, and comparing their function in T-cell proliferation assays with phorbol-12-myristate-13- acetate (PMA), anti-CD3, or IL-2. There was a correlation between conjugate size and proliferation with IL-2, whereas costimulation with PMA or CD3 was optimized at a lower degree of CD28 aggregation. The inositol phospholipid (InsP) generation and increase in [Ca2+]i after CD28 receptor aggregation appeared to proceed through a pathway different from the CD3/T-cell receptor (TCR) pathway since it was enhanced by pretreatment with PMA, while the InsP and [Ca2+]i signal from crosslinking CD3 was suppressed by PMA. Furthermore, the proliferation response to CD28 aggregation was resistant to inhibition by CD3 modulation. Thus, CD28 aggregation appears to trigger a phospholipase C activation pathway that differs from the CD3/TCR-linked pathway.

scholarly journals Palmitylation of an amino-terminal cysteine motif of protein tyrosine kinases p56lck and p59fyn mediates interaction with glycosyl-phosphatidylinositol-anchored proteins.

1993 ◽  
Vol 13 (10) ◽  
pp. 6385-6392 ◽  
Author(s):  
A M Shenoy-Scaria ◽  
L K Gauen ◽  
J Kwong ◽  
A S Shaw ◽  
D M Lublin
Keyword(s):  
Amino Acids ◽  
Cell Line ◽  
Tyrosine Kinases ◽  
Cell Activation ◽  
Mutational Analysis ◽  
Protein Tyrosine Kinases ◽  
Protein Tyrosine ◽  
Glycosyl Phosphatidylinositol ◽  
Amino Terminal ◽  
Cysteine Motif

Cross-linking of glycosyl-phosphatidylinositol (GPI)-anchored membrane proteins on T cells can trigger cell activation. We and others have shown an association between GPI-anchored proteins and the protein tyrosine kinases (PTKs) p56lck and p59fyn, suggesting a pathway for signaling through GPI-anchored proteins. Studies of decay-accelerating factor (DAF) or CD59 in either the C32 cell line or the HeLa cell line transfected with PTK cDNA demonstrated that the GPI-anchored proteins associated noncovalently with p56lck and p59fyn but not with p60src. Nonmyristylated versions of p56lck and p59fyn also failed to associate with the GPI-anchored proteins. Mutational analysis of the PTK demonstrated that the association with the GPI-anchored proteins mapped to the unique amino-terminal domains of the PTK. A chimeric PTK consisting of the 10 amino-terminal residues of p56lck or p59fyn replacing the corresponding amino acids in p60src was sufficient for association with DAF, but the converse constructs containing the first 10 amino acids of p60src plus the remainder of p56lck or p59fyn did not associate with DAF. Mutation of cysteine to serine at positions 3 and 6 in p59fyn or positions 3 and 5 in p56lck abolished the association of these kinases with DAF. Mutation of serine to cysteine at positions 3 and 6 in p60src conferred on p60src the ability to associate with DAF. Direct labeling with [3H]palmitate demonstrated palmitylation of this amino-terminal cysteine motif in p56lck. Thus, palmitylation of the amino-terminal cysteine residue(s) together with myristylation of the amino-terminal glycine residue defines important motifs for the association of PTKs with GPI-anchored proteins.

scholarly journals Itk and Fyn Make Independent Contributions to T Cell Activation

1997 ◽  
Vol 186 (12) ◽  
pp. 2069-2073 ◽  
Author(s):  
X. Charlene Liao ◽  
Dan R. Littman ◽  
Arthur Weiss
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Tyrosine Kinases ◽  
Cell Activation ◽  
Protein Tyrosine Kinases ◽  
Tcr Signaling ◽  
Peripheral T Cells ◽  
Tcr Signal Transduction ◽  
Deficient Mice ◽  
Nonreceptor Protein Tyrosine Kinases

Itk is a member of the Btk/Tec/Itk family of nonreceptor protein tyrosine kinases (PTKs), and has been implicated in T cell antigen receptor (TCR) signal transduction. Lck and Fyn are the Src-family nonreceptor PTKs that are involved in TCR signaling. To address the question of how these members of different families of PTKs functionally contribute to T cell development and to T cell activation, mice deficient for both Itk and either Lck or Fyn were generated. The Itk/Lck doubly deficient mice exhibited a phenotype similar to that of Lck-deficient mice. The phenotype of the Itk/Fyn doubly deficient mice was similar to that of Itk deficient mice. However the Itk/Fyn doubly deficient mice exhibited a more severe defect in TCR-induced proliferation of thymocytes and peripheral T cells than did mice deficient in either kinase alone. These data support the notion that Itk and Fyn both make independent contributions to TCR-induced T cell activation.

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