sq-23377 has been researched along with oxophenylarsine* in 3 studies
3 other study(ies) available for sq-23377 and oxophenylarsine
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Phosphatidylinositol 4-OH kinase is a downstream target of neuronal calcium sensor-1 in enhancing exocytosis in neuroendocrine cells.
Neuronal calcium sensor-1 (NCS-1), the mammalian orthologue of frequenin, belongs to a family of EF-hand-containing Ca(2+) sensors. NCS-1/frequenin has been shown to enhance synaptic transmission in PC12 cells and Drosophila and Xenopus, respectively. However, the precise molecular mechanism for the enhancement of exocytosis is largely unknown. In PC12 cells, NCS-1 potentiated exocytosis evoked by ATP, an agonist to phospholipase C-linked receptors, but had no effect on depolarization-evoked release. NCS-1 also enhanced exocytosis triggered by ionomycin, a Ca(2+) ionophore that bypasses K(+) and Ca(2+) channels. Overexpression of NCS-1 caused a shift in the dose-response curve of inhibition of ATP-evoked secretion using phenylarsine oxide, an inhibitor of phosphatidylinositol 4-OH kinase (PI4K). Plasma membrane phosphatidylinositol 4,5-bisphosphate pools were increased upon NCS-1 transfection as visualized using a phospholipase C-delta pleckstrin homology domain-green fluorescent protein construct. NCS-1-transfected cell extracts displayed increased phosphatidylinositol-4-phosphate biosynthesis, indicating an increase in PI4K activity. Mutations in NCS-1 equivalent to those that abolish the interaction of recoverin, another EF-hand-containing Ca(2+) sensor, with its downstream target rhodopsin kinase, lost their ability to enhance exocytosis. Taken together, the present data indicate that NCS-1 modulates the activity of PI4K, leading to increased levels of phosphoinositides and concomitant enhancement of exocytosis. Topics: 1-Phosphatidylinositol 4-Kinase; Adenosine Triphosphate; Animals; Arsenicals; Calcium Signaling; Calcium-Binding Proteins; Drosophila; Enzyme Inhibitors; Exocytosis; Ionomycin; Membrane Potentials; Neuronal Calcium-Sensor Proteins; Neuropeptides; Neurosecretory Systems; PC12 Cells; Pheochromocytoma; Rats; Type C Phospholipases; Xenopus | 2003 |
A tyrosine phosphorylation requirement for cytotoxic T lymphocyte degranulation.
Phorbol myristate acetate (PMA) plus ionomycin induces the tyrosine phosphorylation of several cytotoxic T lymphocyte (CTL) substrates, including one with an apparent molecular weight of 100,000 (pp100) in cloned murine CTL. cis-Unsaturated fatty acids and low concentrations of phenylarsine oxide specifically inhibit the tyrosine phosphorylation of pp100. Genistein also inhibits tyrosine phosphorylation of pp100, but not with the same specificity as cis-fatty acids or low concentrations of phenylarsine oxide. Degranulation triggered by PMA plus ionomycin is inhibited by cis-fatty acids, low concentrations of phenylarsine oxide, and genistein, under the same conditions that these agents inhibit tyrosine phosphorylation of pp100. Depleting CTL of protein kinase C (PKC) activity by prolonged exposure to PMA eliminates the increase in tyrosine phosphorylation when challenged by PMA plus ionomycin, but not when these PKC-depleted CTL are activated by cognate target cells, immobilized anti-T cell receptor (TCR) antibodies, or concanavalin A. Tyrosine phosphorylation of pp100 triggered by TCR engagement in PKC-depleted cells is inhibited by cis-fatty acids and phenylarsine oxide, indicating that the inhibitory mechanism of the tyrosine phosphorylation of pp100 is independent of PKC. Furthermore, because all three tyrosine phosphorylation inhibitors are unlikely to inhibit PKC, these results suggest that, in addition to PKC activation and a rise in intracellular Ca2+, CTL degranulation requires the tyrosine phosphorylation of a CTL substrate(s), in addition to phospholipase C, and the present results are consistent with pp100 as that substrate. Taken together with previous studies, these results suggest that tyrosine phosphorylation of pp100 may play a central role in CTL function. Topics: Animals; Arsenicals; Calcium; Clone Cells; Concanavalin A; Fatty Acids, Nonesterified; Genistein; Ionomycin; Isoflavones; Kinetics; Lymphocyte Activation; Mice; Molecular Weight; Oleic Acid; Oleic Acids; Phosphoproteins; Phosphotyrosine; Protein Kinase C; Protein-Tyrosine Kinases; T-Lymphocytes, Cytotoxic; Tetradecanoylphorbol Acetate; Tyrosine | 1994 |
Phenylarsine oxide and phorbol myristate acetate inhibit the CD3-induced rise of cytosolic Ca2+ in Jurkat cells by refilling internal Ca2+ stores.
Phenylarsine oxide (PAO), an inhibitor of tyrosine phosphatases, has been found to inhibit the early elevation in cytosolic Ca2+ concentration ([Ca2+]i), related to the CD3 activation pathway in Jurkat T cells. This inhibition was dose-dependent, consistent with previously reported effects of PAO on tyrosine phosphatases, and reversed by dimercaptopropanol. By contrast, okadaic acid, an inhibitor of serine/threonine phosphatases, had no effect on CD3-induced Ca2+ flux. PAO was compared with phorbol 12-myristate 13-acetate (PMA), which caused a similar, although less potent, inhibition as previously described. The two reagents produced additive inhibition of the CD3-induced [Ca2+]i rise, but did not affect thapsigargin- or ionomycin-driven Ca2+ flux in Jurkat cells. PAO and PMA prevented cells from complete depletion of intracellular Ca2+ stores by an anti-CD3 monoclonal antibody (mAb) and restored, at least partially, the ionomycin-sensitive pool, when added after anti-CD3 mAb. Moreover, the CD3-induced inhibition of phosphatidylserine synthesis, due to depletion of internal Ca2+ stores, is reversed by PAO and PMA. Anti-phosphotyrosine immunoblot analysis show that these effects cannot be accounted for by an inhibition of CD3-induced tyrosine phosphorylations. We propose that PAO and, to a lesser extent, PMA allow the refilling of internal compartments by Ca2+, which consequently abrogates a capacitative entry of external Ca2+. Topics: Arsenicals; Biological Transport; Calcium; CD3 Complex; Cell Line; Cytosol; Ethers, Cyclic; Humans; Ionomycin; Okadaic Acid; Phosphatidylserines; Phosphorylation; T-Lymphocytes; Terpenes; Tetradecanoylphorbol Acetate; Thapsigargin; Tyrosine | 1994 |