Fc epsilon RI-mediated tyrosine phosphorylation and activation of the 72-kDa protein-tyrosine kinase, PTK72, in RBL-2H3 rat tumor mast cells.

Hutchcroft, Jill E.; Geahlen, Robert L.; Deanin, Grace G.; Oliver, Janet M.

doi:10.1073/pnas.89.19.9107

Cited by 214 publications

(121 citation statements)

References 23 publications

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“…Engagement of the tetrameric (~fl~'2) FceRI receptors mediates the activation of the non-receptor tyrosine kinases Lyn and Syk [1][2][3][4][5][6]. The activation of these kinases leads to the phosphorylation of various substrates including the fl and ?'…”

Section: Introductionmentioning

confidence: 99%

inhibits antigen‐mediated Syk, but not Lyn tyrosine kinase activation in mast cells

Vallé

Kinét

1995

FEBS Letters

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High affinity IgE receptors (a~/2) mediate the activation of the non-receptor tyrosine kinases Lyn and Syk. Here we show that the antioxidant drug N-acetyl-L-cysteine (NAC) inhibits antigen-mediated Syk activation whereas Lyn activation and phosphorylation of I~ and -/ is maintained. Furthermore, NAC inhibits antigen-mediated calcium mobilization and exocytosis in a dose-dependent manner, but does not inhibit ionomycininduced exocytosis. These data support a model in which the activation of Lyn is responsible for receptor phosphorylation and precedes the activation of Syk. The inhibition of Syk activation by NAC may be relevant to B and T cell antigen receptors, which are also linked to Syk/ZAP'/0 tyrusine kinases.Key words: N-acetyl-L-cysteine; FceRI receptor; tyrosine kinase also suggested that FceRI 7/associates with Syk and are consistent with our model [5,6] Oxidants and antioxidants are being increasingly used in studies of cell function. These include studies on growth regulation [20], apoptosis [21] and HIV-replication [22]. It is now well established that oxidizing conditions induce tyrosine kinase activation and protein phosphorylation [23 26]. However, the effect of antioxidants on tyrosine kinases has not been studied. In this report, we have investigated whether N-acetyl-L-cysteine (NAC), an antioxidant drug which can enter cells readily, could modulate cellular activation. We analyzed the effects of NAC on antigen-mediated protein phosphorylations, tyrosine kinase activation, calcium mobilization and exocytosis.

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Section: Introductionmentioning

confidence: 99%

inhibits antigen‐mediated Syk, but not Lyn tyrosine kinase activation in mast cells

Vallé

Kinét

1995

FEBS Letters

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“…In an attempt to determine which pathways are primarily affected, we first analyzed tyrosine phosphorylation of Syk. This kinase becomes rapidly phosphorylated in Thy-1- [12], TEC-21-[8] or Fc 4 RI- [13] activated RBL cells, and has already been shown to exhibit an increased tyrosine phosphorylation in latrunculinpretreated and Fc 4 RI-activated cells [2]. Immunoblotting analysis showed that phosphorylation of Syk was slightly increased by latrunculin alone, i.e.…”

Section: Early Activation Pathwaysmentioning

confidence: 99%

Involvement of filamentous actin in setting the threshold for degranulation in mast cells

et al. 2004

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Previous studies using cytochalasins and latrunculin B, inhibitors of actin polymerization, showed that filamentous (F)-actin had a negative regulatory role in Fc 4 receptor I (Fc 4 RI) signaling. How F-actin is involved in regulating the activation of mast cells is unknown. In this study we investigated the role of F-actin in mast cell activation induced by aggregation of the glycosylphosphatidylinositol (GPI)-anchored proteins Thy-1 and TEC-21, and compared it to activation via Fc 4 RI. Pretreatment of rat basophilic leukemia cells with latrunculin B inhibited the Thy-1-induced actin polymerization and elevated the Thy-1-mediated secretory and calcium responses. Inhibition of actin polymerization followed by Thy-1 aggregation resulted in an increased tyrosine phosphorylation of Syk, phospholipase C + (PLC + ), Gab2 and linker for activation of T cells (LAT) adapters, and some other signaling molecules. Enzymatic activities of phosphatidylinositol 3-kinase, PLC + , and phosphatase SHP-2 were also upregulated, but tyrosine phosphorylation of ezrin was inhibited. Similar changes were observed in Fc 4 RI-activated cells. Significant changes in intracellular distribution, tyrosine phosphorylation, and/or enzymatic activities of signaling molecules occurred in latrunculinpretreated cells before cell triggering. The combined data suggest that actin polymerization is critical for setting the thresholds for mast cell signaling via aggregation of both Fc 4 RI and GPI-anchored proteins.

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“…In addition to being used as immunosuppressants, mTORC1 inhibitors are evaluated as therapeutic agents in various types of cancer, 5,6 with high efficacy already documented in renal cell carcinoma. 13 Syk is a protein tyrosine kinase expressed in B lymphocytes, 14 monocytes/macrophages, 15 mast cells, 16 and other cell types. Syk has been found to be involved in signal transduction through several types of receptors including the antigen B-cell receptor 17 and at least three different receptors for the Fc component of immunoglobulins G and E. 14 -16,18 -20 A recent report suggests that Syk may be involved in mTORC1 activation in a follicular and possibly other types of B-cell lymphoma.…”

mentioning

confidence: 99%

Activation of mTORC1 Signaling Pathway in AIDS-Related Lymphomas

El-Salem

Raghunath

Marzec

et al. 2009

The American Journal of Pathology

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Using immunohistochemistry with antibodies against the phosphoserine residues in both S6rp and 4E binding protein 1, we identified the activation of the mammalian target of rapamycin (mTORC)1 pathway in 29 cases of AIDS-related lymphoma. These cases represented a diverse spectrum of histological types of nonHodgkin lymphoma (24 cases) and classic Hodgkin lymphoma (five cases). mTORC1 was also activated in the hyperplastic but not involuted follicles of HIV-associated lymphadenopathy in eight cases, supporting the notion that mTORC1 activation is a common feature of transformed lymphocytes irrespective of either their reactive or malignant phenotype. We also found that in B-cell lines that represent diffuse large B-cell lymphoma, Burkitt lymphoma, Epstein-Barr virus-infected lymphocytes, and human herpesvirus 8-positive primary effusion lymphoma, inhibitors of Syk, MEK, and, seemingly , phosphoinositide 3 kinases suppressed mTORC1 activation , in particular when these inhibitors were used in combination. These findings indicate that AIDS-related lymphoma and other histologically similar types of lymphomas that are derived from transformed B lymphocytes may display clinical responses to inhibitors that directly target mTORC1 or , possibly , upstream activators of the mTORC1 pathway.

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Fc epsilon RI-mediated tyrosine phosphorylation and activation of the 72-kDa protein-tyrosine kinase, PTK72, in RBL-2H3 rat tumor mast cells.

Cited by 214 publications

References 23 publications

inhibits antigen‐mediated Syk, but not Lyn tyrosine kinase activation in mast cells

inhibits antigen‐mediated Syk, but not Lyn tyrosine kinase activation in mast cells

Involvement of filamentous actin in setting the threshold for degranulation in mast cells

Activation of mTORC1 Signaling Pathway in AIDS-Related Lymphomas

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