Distinct role of spleen tyrosine kinase in the early phosphorylation of inhibitor of κBα via activation of the phosphoinositide-3-kinase and Akt pathways

Lee, Yong Gyu; Chain, Benjamin M.; Cho, Jae Youl

doi:10.1016/j.biocel.2008.08.011

Cited by 96 publications

(72 citation statements)

References 48 publications

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“…Furthermore, HAD-B markedly inhibited IjBa phosphorylation at 5 min (Fig. 3A), which was predominantly mediated by Syk kinase, 42 strongly supporting a role of Syk as an antiinflammatory target of HAD-B.…”

Section: Fig 3 Effects Of Had-b On Upstream Signaling For Nf-jb Actsupporting

confidence: 57%

“…The extract significantly suppressed activation at 2 and 3 min, as assessed from tyrosine phosphorylation levels of the kinases. 42 The issue of whether the inhibition of tyrosine phosphorylation of both Src and Syk by HAD-B is linked to direct suppression of kinase activity was examined with a kinase assay using purified Syk or Src. Intriguingly, HAD-B suppressed the kinase activity of Syk, but not that of Src, suggesting that some of the components in HAD-B act as direct Syk kinase inhibitor(s), while HAD-B-mediated inhibition of Src phosphorylation is indirectly triggered.…”

Section: Fig 1 Effect Of Had-b On Inflammatory Responses In Vitro mentioning

confidence: 99%

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HangAmDan-B, an Ethnomedicinal Herbal Mixture, Suppresses Inflammatory Responses by Inhibiting Syk/NF-κB and JNK/ATF-2 Pathways

Moh

Kim

et al. 2013

Journal of Medicinal Food

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HangAmDan-B (HAD-B) is a powdered mixture of eight ethnopharmacologically characterized folk medicines that is prescribed for solid masses and cancers in Korea. In view of the finding that macrophage-mediated inflammation is a pathophysiologically important phenomenon, we investigated whether HAD-B modulates inflammatory responses and explored the associated molecular mechanisms. The immunomodulatory activity of HAD-B in toll-like receptor-activated macrophages induced by lipopolysaccharide (LPS) was assessed by measuring nitric oxide (NO) and prostaglandin E2 (PGE2) levels. To identify the specific transcription factors (such as nuclear factor [NF]-jB and signaling enzymes) targeted by HAD-B, biochemical approaches, including kinase assays and immunoblot analysis, were additionally employed. HAD-B suppressed the production of PGE2 and NO in LPS-activated macrophages in a dose-dependent manner. Furthermore, the extract ameliorated HCl/EtOH-induced gastritis symptoms. Moreover, HAD-B significantly inhibited LPS-induced mRNA expression of inducible NO synthase and cyclooxygenase (COX)-2. Interestingly, marked inhibition of NF-jB and activating transcription factor was observed in the presence of HAD-B. Data from direct kinase assays and immunoblot analysis showed that HAD-B suppresses activation of the upstream signaling cascade involving spleen tyrosine kinase, Src, p38, c-Jun N-terminal kinase, and transforming growth factor b-activated kinase 1. Finally, kaempferol, but not quercetin or resveratrol was identified as a bioactive compound in HAD-B. Therefore, our results suggest that HAD-B possesses anti-inflammatory activity that contributes to its anticancer property.

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Section: Fig 3 Effects Of Had-b On Upstream Signaling For Nf-jb Actsupporting

confidence: 57%

Section: Fig 1 Effect Of Had-b On Inflammatory Responses In Vitro mentioning

confidence: 99%

HangAmDan-B, an Ethnomedicinal Herbal Mixture, Suppresses Inflammatory Responses by Inhibiting Syk/NF-κB and JNK/ATF-2 Pathways

Moh

Kim

et al. 2013

Journal of Medicinal Food

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“…48 In leukemic cells, PI3K activity depends on activation of upstream signaling components, such as SYK. 49 The phosphorylation status of Akt reflects PI3K activity as a direct target. Our analyses revealed that SYK inhibition by R406 is sufficient to almost completely abrogate PI3K activity induced by various microenvironmental stimuli.…”

Section: Discussionmentioning

confidence: 99%

Spleen tyrosine kinase inhibition prevents chemokine- and integrin-mediated stromal protective effects in chronic lymphocytic leukemia

Buchner

Baer

Prinz

et al. 2010

Blood

159

108

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“…Semi-quantitative RT reactions were conducted using MuLV reverse transcriptase as reported previously (Lee et al, 2009). The primers (Bioneer, Seoul, Korea) used in this experiment are indicated in Table I (F: forward, R: reverse).…”

Section: Rt-pcrmentioning

confidence: 99%

Extracellular Signal-Regulated Kinase Is a Major Enzyme in Korean Mistletoe Lectin-Mediated Regulation of Macrophage Functions

Byeon¹,

Lee²,

Yu³

et al. 2009

Biomolecules and Therapeutics

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-Korean mistletoe lectin (KML) is the major component found in Viscum album var. (coloratum), displaying anti-cancer and immunostimulating activities. Even though it has been shown to boost host immune defense mechanisms, the regulatory roles of KML on the functional activation of macrophages have not been fully elucidated. In this study, regulatory mechanism of KML on macrophage-mediated immune responses was examined in terms of KML-mediated signaling event. KML clearly induced mRNA expression of tumor necrosis factor (TNF)-α, the generation of reactive oxygen species (ROS) and phagocytic uptake in RAW264.7 cells. All of these events were strongly suppressed by U0126, whereas TNF-α mRNA was not diminished by SB203580 and SP600125, indicating ERK as a central enzyme managing KML-induced up-regulation of macrophage functions. Indeed, KML strongly induced the phosphorylation of ERK in a time-dependent manner without altering its total level. Therefore, these data suggest that ERK may be a major signaling enzyme with regulatory property toward various KML-mediated macrophage responses.

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Distinct role of spleen tyrosine kinase in the early phosphorylation of inhibitor of κBα via activation of the phosphoinositide-3-kinase and Akt pathways

Cited by 96 publications

References 48 publications

HangAmDan-B, an Ethnomedicinal Herbal Mixture, Suppresses Inflammatory Responses by Inhibiting Syk/NF-κB and JNK/ATF-2 Pathways

HangAmDan-B, an Ethnomedicinal Herbal Mixture, Suppresses Inflammatory Responses by Inhibiting Syk/NF-κB and JNK/ATF-2 Pathways

Spleen tyrosine kinase inhibition prevents chemokine- and integrin-mediated stromal protective effects in chronic lymphocytic leukemia

Extracellular Signal-Regulated Kinase Is a Major Enzyme in Korean Mistletoe Lectin-Mediated Regulation of Macrophage Functions

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