Search results for "Phosphoprotein Phosphatases"
showing 10 items of 20 documents
Phosphoproteins Involved in the Signal Transduction of Cryptogein, an Elicitor of Defense Reactions in Tobacco
2000
We previously reported that the signal transduction of cryptogein, an elicitor of defense reactions in Nicotiana tabacum cells, involves upstream protein phosphorylation. In the present study, induction of these early physiological events was further investigated with inhibitors of protein phosphatase (PP), okadaïc acid, and calyculin A. Calyculin A mimicked the effects of cryptogein, inducing an influx of calcium, an extracellular alkalinization, and the production of active oxygen species (AOS), suggesting that during cryptogein signal transduction the balance between specific protein kinase (PK) and PP activities was modified. To identify the phosphorylated proteins that could be involv…
Fine-Tuning of Platelet Responses by Serine/Threonine Protein Kinases and Phosphatases-Just the Beginning.
2021
AbstractComprehensive proteomic analyses of human and murine platelets established an extraordinary intracellular repertoire of signaling components, which control crucial functions. The spectrum of platelet serine/threonine protein kinases (more than 100) includes the AGC family (protein kinase A, G, C [PKA, PKG, PKC]), the mitogen-activated protein kinases (MAPKs), and others. PKA and PKG have multiple significantly overlapping substrates in human platelets, which possibly affect functions with clear “signaling nodes” of regulation by multiple protein kinases/phosphatases. Signaling nodes are intracellular Ca2+ stores, the contractile system (myosin light chains), and other signaling comp…
Cytoplasmic localization of the cell polarity factor scribble supports liver tumor formation and tumor cell invasiveness
2018
The loss of epithelial cell polarity plays an important role in the development and progression of liver cancer. However, the specific molecular mechanisms supporting tumor initiation and progression are poorly understood. In this study, transcriptome data and immunofluorescence stains of tissue samples derived from hepatocellular carcinoma (HCC) patients revealed that overexpression associated with cytoplasmic localization of the baso-lateral cell polarity complex protein Scribble (Scrib) correlated with poor prognosis of HCC patients. In comparison to HCC cells stably expressing wildtype Scrib (ScribWT), mutated Scrib with enforced cytoplasmic enrichment (ScribP305L) induced AKT signaling…
Cold stress defense in the freshwater sponge Lubomirskia baicalensis
2007
The endemic freshwater sponge Lubomirskia baicalensis lives in Lake Baikal in winter (samples from March have been studied) under complete ice cover at near 0 degrees C, and in summer in open water at 17 degrees C (September). In March, specimens show high metabolic activity as reflected by the production of gametes. L. baicalensis lives in symbiosis with green dinoflagellates, which are related to Gymnodinium sanguineum. Here we show that these dinoflagellates produce the toxin okadaic acid (OA), which is present as a free molecule as well as in a protein-bound state. In metazoans OA inhibits both protein phosphatase-2A and protein phosphatase-1 (PP1). Only cDNA corresponding to PP1 could …
Role of Gadd45a in Wip1-dependent regulation of intestinal tumorigenesis.
2012
Conversion of intestinal stem cells into tumor-initiating cells is an early step in Apc(Min)-induced polyposis. Wild-type p53-induced phosphatase 1 (Wip1)-dependent activation of a DNA damage response and p53 has a permanent role in suppression of stem cell conversion, and deletion of Wip1 lowers the tumor burden in Apc(Min) mice. Here we show that cyclin-dependent kinase inhibitor 2a, checkpoint kinase 2, and growth arrest and DNA damage gene 45a (Gadd45a) exert critical functions in the tumor-resistant phenotype of Wip1-deficient mice. We further identified Gadd45a as a haploinsufficient gene in the regulation of Wip1-dependent tumor resistance in mice. Gadd45a appears to function through…
Cross-talk between oxidative stress and pro-inflammatory cytokines in acute pancreatitis: a key role for protein phosphatases.
2009
Acute pancreatitis is an acute inflammatory process localized in the pancreatic gland that frequently involves peripancreatic tissues. It is still under investigation why an episode of acute pancreatitis remains mild affecting only the pancreas or progresses to a severe form leading to multiple organ failure and death. Proinflammatory cytokines and oxidative stress play a pivotal role in the early pathophysiological events of the disease. Cytokines such as interleukin 1beta and tumor necrosis factor alpha initiate and propagate almost all consequences of the systemic inflammatory response syndrome. On the other hand, depletion of pancreatic glutathione is an early hallmark of acute pancreat…
Integrin alpha 2 beta 1 promotes activation of protein phosphatase 2A and dephosphorylation of Akt and glycogen synthase kinase 3 beta.
2002
The integrins are a large family of heterodimeric transmembrane receptors composed of α and β subunits (22). In addition to mediating cell-matrix interactions, integrins have been shown to activate intracellular signaling pathways which, in collaboration with growth factor-induced signals, regulate cellular functions (46). Some integrin signaling cascades are activated via the β subunit cytoplasmic domain, and they are therefore triggered by several integrin heterodimers. These signals include the activation of protein tyrosine kinases of the Src and focal adhesion kinase (FAK) families (9, 47). More-recent studies have revealed signaling events that are activated specifically by an α subun…
Use of CDC2 from etoposide-treated cells as substrate to assay CDC25 phosphatase activity
1999
International audience; Cyclin-dependent kinases (CDKs) regulate the key transition of the cell cycle in all organisms. In response to Etoposide (VP-16) induced DNA damage, cells undergo a G2-phase arrest resulting in the accumulation of inactive CDK1 (CDC2) kinase complexes. Here we report that upon Etoposide treatment CDC2 is phosphorylated on tyrosine 15 and is dephosphorylated and activated in vitro by recombinant CDC25 phosphatase. We also show that inactive CDC2 kinase from Etoposide-treated cells can be used as a substrate in a sensitive two-step assay of CDC25 phosphatase. This assay, which is very simple to set-up, is based on the monitoring of CDC2 kinase activity after CDC25-depe…
cAMP-dependent phosphorylation of CYP2B1 as a functional switch for cyclophosphamide activation and its hormonal controlin vitro andin vivo
2001
An important feature of cytochrome P450 (CYP) 2B1 is its high ability to convert the prodrug cyclophosphamide (CPA) to therapeutically cytotoxic metabolites, resulting in interstrand DNA-cross-linking and cell death. We have examined whether and how the phosphorylation of CYP2B1 influences CPA metabolic activation in vitro and in vivo. We found first that only part of the total CYP2B1 pool undergoes phosphorylation. This part is fully inactivated. Second, phosphorylation of CYP2B1 in intact hepatocytes reduced by up to 75% toxification of CPA to mutagenic metabolites (totally dependent on the same preferentially CYP2B-catalyzed 4-hydroxylation of CPA as is the generation of highly cytotoxic…
Pentoxifylline Prevents Loss of PP2A Phosphatase Activity and Recruitment of Histone Acetyltransferases to Proinflammatory Genes in Acute Pancreatitis
2009
Mitogen-activated protein kinases (MAPKs) are considered major signal transducers early during the development of acute pancreatitis. Pentoxifylline is a phosphodiesterase inhibitor with marked anti-inflammatory properties through blockade of extracellular signal regulated kinase (ERK) phosphorylation and tumor necrosis factor alpha production. Our aim was to elucidate the mechanism of action of pentoxifylline as an anti-inflammatory agent in acute pancreatitis. Necrotizing pancreatitis induced by taurocholate in rats and taurocholate-treated AR42J acinar cells were studied. Phosphorylation of ERK and ERK kinase (MEK1/2), as well as PP2A, PP2B, and PP2C serine/threonine phosphatase activiti…