Rac mediates cytoskeletal rearrangements and increased cell motility induced by urokinase-type plasminogen activator receptor binding to vitronectin.
AuthorsKjøller L, Hall A
JournalJ Cell Biol
PubMed ID11257116
'The urokinase-type plasminogen activator receptor (uPAR) is involved in the regulation of cell motility in a variety of cell types. We show here that expression of human uPAR in growing murine fibroblasts leads to a dramatic reorganization of the actin cytoskeleton. uPAR expression induces multiple rapidly advancing protrusions that resemble ... More
Regulation of alphaIIb beta3 function in human B lymphocytes.
AuthorsQi W, Loh E, Vilaire G, Bennett JS
JournalJ Biol Chem
PubMed ID9614143
'We studied the function of the platelet integrin alphaIIb beta3 using a B lymphocyte model in which alphaIIb beta3 can be induced to interact with fibrinogen using phorbol myristate acetate (PMA). To determine whether a G protein-coupled receptor could also activate alphaIIb beta3 in lymphocytes, we coexpressed the human formyl ... More
Muscarinic acetylcholine receptor-mediated induction of zif268 mRNA in PC12D cells requires protein kinase C and the influx of extracellular calcium.
AuthorsEbihara T, Saffen D
JournalJ Neurochem
PubMed ID9048745
'The immediate-early gene zif268 (egr-1, NGFI-A, krox-24) encodes a transcription factor that has been proposed to play a role in differentiation and neuronal plasticity. zif268 mRNA is undetectable in unstimulated PC12D cells, a subline of PC12 characterized by accelerated differentiation in the presence of nerve growth factor, but is rapidly ... More
Phosphorylation and regulation of antidepressant-sensitive serotonin transporters.
AuthorsRamamoorthy S, Giovanetti E, Qian Y, Blakely RD
JournalJ Biol Chem
PubMed ID9442097
'Antidepressant-sensitive serotonin (5-hydroxytryptamine, 5HT) transporters (SERTs) are responsible for efficient synaptic clearance of extracellular 5HT. Previously (Qian, Y., Galli, A., Ramamoorthy, S., Risso, S., DeFelice, L. J., and Blakely, R. D. (1997) J. Neurosci. 17, 45-47), we demonstrated that protein kinase (PKC)-linked pathways in transfected HEK-293 cells lead to the ... More
Tobacco smoke tumor promoters, catechol and hydroquinone, induce oxidative regulation of protein kinase C and influence invasion and metastasis of lung carcinoma cells.
AuthorsGopalakrishna R, Chen ZH, Gundimeda U
JournalProc Natl Acad Sci U S A
PubMed ID7991611
'Cigarette smoke polyphenolic agents (catechol and hydroquinone) that generate oxidants have been shown to be tumor promoters. Furthermore, oxidants can influence protein kinase C (PKC)-mediated signal transduction. Since terpenoid tumor promoters, phorbol esters, increase invasion and metastasis by activating PKC, we have determined whether polyphenolic agents present in the cigarette ... More
Regulation of mRNA encoding 5-HT2A receptors in P11 cells through a post-transcriptional mechanism requiring activation of protein kinase C.
'Exposure of P11 cells to serotonin (5-HT) resulted in a transient increase in levels of 5-HT2A receptor mRNA. Exposure to 5-HT for as short a time as 1 min was sufficient to trigger a delayed increase in receptor mRNA. 5-HT-induced increases in receptor mRNA levels were not antagonized by the ... More
Tyrosine phosphorylation-dependent stimulation of amyloid precursor protein secretion by the m3 muscarinic acetylcholine receptor.
AuthorsSlack BE, Breu J, Petryniak MA, Srivastava K, Wurtman RJ
JournalJ Biol Chem
PubMed ID7713942
'Stimulation of m1 and m3 muscarinic acetylcholine receptors, which are coupled to phosphoinositide hydrolysis and protein kinase C activation, has been shown to increase the release of soluble amyloid precursor protein derivatives (APPs). The effect is mimicked by phorbol esters, which directly activate protein kinase C. Using human embryonic kidney ... More
The role of cytosolic Ca2+, protein kinase C, and protein kinase A in hormonal stimulation of phospholipase D in rat hepatocytes.
'Ca(2+)-dependent and protein kinase C-dependent mechanisms of phospholipase D (PLD) activation were studied in rat hepatocytes by measuring phosphatidylethanol (Peth) formation in the presence of ethanol. Stimulation of Peth formation by 12-O-tetradecanoyl-phorbol 13-acetate (TPA), vasopressin, or A23187 was inhibited by multiple protein kinase C inhibitors or by protein kinase C ... More
Suppression of ceramide-mediated programmed cell death by sphingosine-1-phosphate.
AuthorsCuvillier O, Pirianov G, Kleuser B, Vanek PG, Coso OA, Gutkind S, Spiegel S
JournalNature
PubMed ID8657285
'Ceramide is an important regulatory participant of programmed cell death (apoptosis) induced by tumour-necrosis factor (TNF)-alpha and Fas ligand, members of the TNF superfamily. Conversely, sphingosine and sphingosine-1-phosphate, which are metabolites of ceramide, induce mitogenesis and have been implicated as second messengers in cellular proliferation induced by platelet-derived growth factor ... More
Formyl peptide receptor signaling in HL-60 cells through sphingosine kinase.
AuthorsAlemany R, Meyer zu Heringdorf D, van Koppen CJ, Jakobs KH
JournalJ Biol Chem
PubMed ID9933590
'Sphingosine-1-phosphate (SPP) produced from sphingosine by sphingosine kinase has recently been reported to act as intracellular second messenger for a number of plasma membrane receptors. In the present study, we investigated whether the sphingosine kinase/SPP pathway is involved in cellular signaling of the Gi protein-coupled formyl peptide receptor in myeloid ... More
Transcription factor phosphorylation by pp90(rsk2). Identification of Fos kinase and NGFI-B kinase I as pp90(rsk2).
AuthorsSwanson KD, Taylor LK, Haung L, Burlingame AL, Landreth GE
JournalJ Biol Chem
PubMed ID9920881
'The in vitro phosphorylation of transcription factors by growth factor-activated protein kinases has resulted in the discovery of a number of activities whose identities and relationships to one another are unclear. Fos kinase is a growth factor-stimulated serine/threonine protein kinase that phosphorylates c-Fos at serine 362 within the carboxyl-terminal regulatory ... More
Thapsigargin-induced degranulation of mast cells is dependent on transient activation of phosphatidylinositol-3 kinase.
AuthorsHuber M, Hughes MR, Krystal G
JournalJ Immunol
PubMed ID10861044
'Thapsigargin, which elevates cytosolic calcium levels by inhibiting the sarcoplasmic/endoplasmic reticulum calcium-dependent ATPase, was tested for its ability to degranulate bone marrow-derived mast cells (BMMCs) from src homology 2-containing inositol phosphatase +/+ (SHIP+/+) and SHIP-/- mice. As was found previously with steel factor, thapsigargin stimulated far more degranulation in SHIP-/- ... More
Role of phospholipase Cbeta3 phosphorylation in the desensitization of cellular responses to platelet-activating factor.
AuthorsAli H, Fisher I, Haribabu B, Richardson RM, Snyderman R
JournalJ Biol Chem
PubMed ID9115222
'Platelet-activating factor (PAF) stimulates a diverse array of cellular responses through receptors coupled to G proteins that activate phospholipase C (PLC). Truncation of the cytoplasmic tail of the receptor to remove phosphorylation sites (mutant PAF receptor, mPAFR) results in enhancement of PAF-stimulated responses. Here we demonstrate that PAF or phorbol ... More
Inhibitors of protein kinase C. 2. Substituted bisindolylmaleimides with improved potency and selectivity.
AuthorsDavis PD, Elliott LH, Harris W, Hill CH, Hurst SA, Keech E, Kumar MK, Lawton G, Nixon JS, Wilkinson SE
JournalJ Med Chem
PubMed ID1552513
'A hypothetical mode of inhibition of protein kinase C (PKC) by the natural product staurosporine has been used as a basis for the design of substituted bisindolylmaleimides with improved potency over the parent compound. Structure-activity relationships were consistent with the interaction of a cationic group in the inhibitor with a ... More
Phosphorylation and subcellular redistribution of pleckstrin in human neutrophils.
AuthorsBrumell JH, Craig KL, Ferguson D, Tyers M, Grinstein S
JournalJ Immunol
PubMed ID9144502
'Pleckstrin, originally described as a major substrate of protein kinase C (PKC) in platelets, was found to be highly expressed in human neutrophils (intracellular concentration, approximately 15 microM). As PKC isoforms play an important role in mediating neutrophil antimicrobial responses, we studied the regulation of pleckstrin phosphorylation in response to ... More
Ras-dependent mitogen-activated protein kinase activation by G protein-coupled receptors. Convergence of Gi- and Gq-mediated pathways on calcium/calmodulin, Pyk2, and Src kinase.
AuthorsDella Rocca GJ, van Biesen T, Daaka Y, Luttrell DK, Luttrell LM, Lefkowitz RJ
JournalJ Biol Chem
PubMed ID9235901
'Many receptors that couple to heterotrimeric guanine-nucleotide binding proteins (G proteins) have been shown to mediate rapid activation of the mitogen-activated protein kinases Erk1 and Erk2. In different cell types, the signaling pathways employed appear to be a function of the available repertoire of receptors, G proteins, and effectors. In ... More
Feedback modulation of ligand-engaged alpha L/beta 2 leukocyte integrin (LFA-1) by cyclic AMP-dependent protein kinase.
AuthorsRovere P, Inverardi L, Bender JR, Pardi R
JournalJ Immunol
PubMed ID8690918
'Rapid interconversion between a firmly adherent and a nonadherent, circulating phenotype is a distinctive feature of mature leukocytes and is thought to be essential for efficient immune surveillance. Leukocyte adhesion is a finely regulated process controlled in part by reversible, activation-dependent up-regulation of beta 1- and beta 2- integrin function. ... More
Phosphorylation of the cAMP response element-binding protein and activation of transcription by alpha1 adrenergic receptors.
AuthorsLin RZ, Chen J, Hu ZW, Hoffman BB
JournalJ Biol Chem
PubMed ID9792725
'Activation of alpha1 adrenergic receptors not only stimulates smooth muscle contraction but also modifies gene expression. We wondered if alpha1 adrenergic receptors could activate transcription of genes regulated by the cAMP response element-binding protein (CREB). Using Rat1 cells stably transfected with each of the three cloned human alpha1 adrenergic receptor ... More
N-Methyl-D-aspartate receptor stimulation activates tyrosinase and promotes melanin synthesis in the ink gland of the cuttlefish Sepia officinalis through the nitric Oxide/cGMP signal transduction pathway. A novel possible role for glutamate as physiologic activator of melanogenesis.
AuthorsPalumbo A, Poli A, Di Cosmo A, d'Ischia M
JournalJ Biol Chem
PubMed ID10748137
'The tyrosinase-catalyzed conversion of l-tyrosine to melanin represents the most distinctive biochemical pathway in the ink gland of the cuttlefish Sepia officinalis; however, the molecular mechanisms underlying its activation have remained so far largely uncharted. In this paper we demonstrate for the first time that l-glutamate can stimulate tyrosinase activity ... More
Both alpha 1A- and alpha 2A-adrenoreceptor subtypes stimulate voltage-operated L-type calcium channels in rat portal vein myocytes. Evidence for two distinct transduction pathways.
AuthorsLeprêtre N, Mironneau J, Morel JL
JournalJ Biol Chem
PubMed ID7961939
'Previously, we have shown that myocytes from rat portal vein express alpha 1A-adrenoreceptors that couple with a Gq/G11-protein to stimulate phosphoinositide turnover and release of calcium from intracellular stores. The purpose of this study was to investigate the contribution of both alpha 1- and alpha 2-adrenoreceptor subtypes in inducing stimulation ... More
Regulation of recombinant cardiac cystic fibrosis transmembrane conductance regulator chloride channels by protein kinase C.
AuthorsYamazaki J, Britton F, Collier ML, Horowitz B, Hume JR
JournalBiophys J
PubMed ID10096895
'We investigated the regulation of cardiac cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channels by protein kinase C (PKC) in Xenopus oocytes injected with cRNA encoding the cardiac (exon 5-) CFTR Cl- channel isoform. Membrane currents were recorded using a two-electrode voltage clamp technique. Activators of PKC or a cAMP ... More
Comparison of staurosporine and four analogues: their effects on growth, rhodamine 123 retention and binding to P-glycoprotein in multidrug-resistant MCF-7/Adr cells.
AuthorsBudworth J, Davies R, Malkhandi J, Gant TW, Ferry DR, Gescher A
JournalBr J Cancer
PubMed ID8624264
'The potent kinase inhibitor staurosporine and its protein kinase C (PKC)-selective analogue CGP 41251 are known to sensitise cells with the multidrug resistance (MDR) phenotype mediated by P-glycoprotein (P-gp) to cytotoxic agents. Here four PKC-selective staurosporine cogeners, CGP 41251, UCN-01, RO 31 8220 and GF 109203X, were compared with staurosporine ... More
Characterisation of the rat SK4/IK1 K(+) channel.
Authorsvon Hahn T, Thiele I, Zingaro L, Hamm K, Garcia-Alzamora M, Köttgen M, Bleich M, Warth R
JournalCell Physiol Biochem
PubMed ID11509830
'BACKGROUND AND AIMS: The Ca(2+)-activated K(+) channel rSK4 is the rat homologue of the human SK4/IK1 (KCNN4) channel. In colonic mucosa rSK4 plays a key role during acetylcholin-induced secretion. This study was aimed to characterize the properties of the rat SK4 channel. METHODS: Electrophysiological measurements were performed on rSK4 expressing ... More
Inhibition of phosphatidylcholine biosynthesis following induction of apoptosis in HL-60 cells.
AuthorsAnthony ML, Zhao M, Brindle KM
JournalJ Biol Chem
PubMed ID10391908
Induction of apoptosis in HL-60 cells, using a variety of cytotoxic drugs, resulted, in all cases, in inhibition of CDP-choline:1, 2-diacylglycerol choline phosphotransferase, leading to an accumulation of its substrate, CDP-choline, and inhibition of phosphatidylcholine biosynthesis. Incubation of the cells with phosphatidylcholine reduced the number displaying an apoptotic morphology following ... More
The specific bisindolylmaleimide PKC-inhibitor GF 109203X efficiently modulates MRP-associated multiple drug resistance.
The newly identified drug transporter MRP is functionally linked to a multiple drug resistance independent from P-glycoprotein. Resistance modifiers for this type of MDR are rare at present. We analyzed the modulating effect of the highly selective bisindolylmaleimide PKC inhibitor GF 109203X on the MRP overexpressing human MDR sublines HL60/AR ... More
Activation of p38 and c-Jun N-terminal kinase pathways and induction of apoptosis by chelerythrine do not require inhibition of protein kinase C.
AuthorsYu R, Mandlekar S, Tan TH, Kong AN
JournalJ Biol Chem
PubMed ID10734112
Chelerythrine, a natural benzophenanthridine alkaloid, has been reported to mediate a variety of biological activities, including inhibition of protein kinase C (PKC). Here we report that chelerythrine induced time- and dose-dependent activation of JNK1 and p38 in HeLa cells, which was mediated the upstream kinases, MEKK1 and MKK4. However, treatment ... More
Integrin leukocyte function-associated antigen-1-mediated cell binding can be activated by clustering of membrane rafts.
AuthorsKrauss K, Altevogt P
JournalJ Biol Chem
PubMed ID10601245
The leukocyte function-associated antigen-1 (LFA-1) integrin (CD11a/CD18) is an important adhesion molecule for lymphocyte migration and the initiation of an immune response. At the cell surface, LFA-1 activity can be regulated by divalent cations that enhance receptor affinity but also by membrane clustering induced by treatment of cells with substances ... More
Integrins regulate the linkage between upstream and downstream events in G protein-coupled receptor signaling to mitogen-activated protein kinase.
AuthorsShort SM, Boyer JL, Juliano RL
JournalJ Biol Chem
PubMed ID10777598
Receptor tyrosine kinases (RTKs) and G protein-coupled receptors (GPCRs) can both activate mitogen-activated protein kinase (MAPK), a critical intermediate in the transduction of proliferative signals. Numerous observations have demonstrated that integrin-mediated cell anchorage can regulate the efficiency of signaling from RTKs to MAPK. Recently, a relationship between integrins and GPCR ... More
Nitric oxide inhibits angiotensin II-induced activation of the calcium-sensitive tyrosine kinase proline-rich tyrosine kinase 2 without affecting epidermal growth factor receptor transactivation.
AuthorsWang D, Yu X, Brecher P
JournalJ Biol Chem
PubMed ID10446212
In a previous study, we showed that nitric oxide donors and N-acetylcysteine, either alone or in combination, inhibited the activation of several mitogen-activated protein kinases by angiotensin II in rat cardiac fibroblasts (Wang, D., Yu, X., and Brecher, P. (1998) J. Biol. Chem. 273, 33027-33034). In the present study, we ... More
Roles of insulin receptor substrate-1, phosphatidylinositol 3-kinase, and release of intracellular Ca2+ stores in insulin-stimulated insulin secretion in beta -cells.
The signaling pathway by which insulin stimulates insulin secretion and increases in intracellular free Ca(2+) concentration ([Ca(2+)](i)) in isolated mouse pancreatic beta-cells and clonal beta-cells was investigated. Application of insulin to single beta-cells resulted in increases in [Ca(2+)](i) that were of lower magnitude, slower onset, and longer lifetime than that ... More
Gbeta gamma mediate differentiation of vascular smooth muscle cells.
AuthorsReusch HP, Schaefer M, Plum C, Schultz G, Paul M
JournalJ Biol Chem
PubMed ID11279222
Proliferation and subsequent dedifferentiation of vascular smooth muscle (VSM) cells contribute to the pathogenesis of atherosclerosis and postangioplastic restenosis. The dedifferentiation of VSM cells in vivo or in cell culture is characterized by a loss of contractile proteins such as smooth muscle-specific alpha-actin and myosin heavy chain (SM-MHC). Serum increased ... More
Actin-dependent propulsion of endosomes and lysosomes by recruitment of N-WASP.
AuthorsTaunton J, Rowning BA, Coughlin ML, Wu M, Moon RT, Mitchison TJ, Larabell CA
JournalJ Cell Biol
PubMed ID10662777
We examined the spatial and temporal control of actin assembly in living Xenopus eggs. Within minutes of egg activation, dynamic actin-rich comet tails appeared on a subset of cytoplasmic vesicles that were enriched in protein kinase C (PKC), causing the vesicles to move through the cytoplasm. Actin comet tail formation ... More
Chemotactic peptide N-formyl-met-leu-phe activation of p38 mitogen-activated protein kinase (MAPK) and MAPK-activated protein kinase-2 in human neutrophils.
AuthorsKrump E, Sanghera JS, Pelech SL, Furuya W, Grinstein S
JournalJ Biol Chem
PubMed ID8995385
Activation of polymorphonuclear leukocytes (PMN) by chemotactic peptides initiates a series of functional responses that serve to eliminate pathogens. The intermediate steps that link engagement of the chemoattractant receptor to the microbicidal responses involve protein kinases that have yet to be identified. In this study we detected in human PMN ... More
Platelet shape change is mediated by both calcium-dependent and -independent signaling pathways. Role of p160 Rho-associated coiled-coil-containing protein kinase in platelet shape change.
AuthorsPaul BZ, Daniel JL, Kunapuli SP
JournalJ Biol Chem
PubMed ID10497186
Platelets undergo shape change upon activation with agonists. During shape change, disc-shaped platelets turn into spiculated spheres with protruding filopodia. When agonist-induced cytosolic Ca(2+) increases were prevented using the cytosolic Ca(2+) chelator, 5, 5'-dimethyl-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (5, 5'-dimethyl-BAPTA), platelets still underwent shape change, although the onset was delayed and the initial ... More
Lysophosphatidic acid activates NF-kappaB in fibroblasts. A requirement for multiple inputs.
AuthorsShahrestanifar M, Fan X, Manning DR
JournalJ Biol Chem
PubMed ID9920937
Lysophosphatidic acid (LPA) is a growth factor that exerts a number of well characterized biological actions on fibroblasts and other cells. In the present study, we investigated the possibility that LPA activates the transcription factor NF-kappaB. NF-kappaB is a target of cytokines, but its activation by other classes of agonists ... More
Muscarinic receptor stimulation increases regulators of G-protein signaling 2 mRNA levels through a protein kinase C-dependent mechanism.
AuthorsSong L, De Sarno P, Jope RS
JournalJ Biol Chem
PubMed ID10514440
RGS2, a member of the Regulators of G-protein Signaling family, modulates the activity of G-proteins coupled to the phosphoinositide signal transduction system, but little is known about what regulates RGS2. In human neuroblastoma SH-SY5Y cells stimulation of muscarinic receptors by carbachol activates phosphoinositide signaling and also caused a rapid, large, ... More
Divergent signaling pathways requiring discrete calcium signals mediate concurrent activation of two mitogen-activated protein kinases by gonadotropin-releasing hormone.
AuthorsMulvaney JM, Roberson MS
JournalJ Biol Chem
PubMed ID10799494
Receptors coupled to heterotrimeric G proteins are linked to activation of mitogen-activated protein kinases (MAPKs) via receptor- and cell-specific mechanisms. We have demonstrated recently that gonadotropin-releasing hormone (GnRH) receptor occupancy results in activation of extracellular signal-regulated kinase (ERK) through a mechanism requiring calcium influx through L-type calcium channels in alphaT3-1 ... More
Chemotactic peptide-induced activation of MEK-2, the predominant isoform in human neutrophils. Inhibition by wortmannin.
AuthorsDowney GP, Butler JR, Brumell J, Borregaard N, Kjeldsen L, Sue-A-Quan AK, Grinstein S
JournalJ Biol Chem
PubMed ID8702863
Exposure of neutrophils to a variety of agonists including chemoattractant peptides and cytokines induces degranulation and activation of the oxidative burst which are required for bacterial killing. The signaling pathways regulating these important functions are incompletely characterized. Mitogen-activated protein (MAP) kinases, which include the extracellular signal-regulated kinases (ERKs), are activated ... More
TGF-beta induced transdifferentiation of mammary epithelial cells to mesenchymal cells: involvement of type I receptors.
AuthorsMiettinen PJ, Ebner R, Lopez AR, Derynck R
JournalJ Cell Biol
PubMed ID7806579
The secreted polypeptide transforming growth factor-beta (TGF-beta) exerts its multiple activities through type I and II cell surface receptors. In epithelial cells, activation of the TGF-beta signal transduction pathways leads to inhibition of cell proliferation and an increase in extracellular matrix production. TGF-beta is widely expressed during development and its ... More
Phosphatidylinositol 3-kinase-dependent membrane association of the Bruton's tyrosine kinase pleckstrin homology domain visualized in single living cells.
AuthorsVárnai P, Rother KI, Balla T
JournalJ Biol Chem
PubMed ID10196179
Phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) has been proposed to act as a second messenger to recruit regulatory proteins to the plasma membrane via their pleckstrin homology (PH) domains. The PH domain of Bruton's tyrosine kinase (Btk), which is mutated in the human disease X-linked agammaglobulinemia, has been shown to interact with PI(3,4,5)P3 ... More
Prostacyclin and sodium nitroprusside inhibit the activity of the platelet inositol 1,4,5-trisphosphate receptor and promote its phosphorylation.
AuthorsCavallini L, Coassin M, Borean A, Alexandre A
JournalJ Biol Chem
PubMed ID8621413
Prostaglandin I2 (PGI2) and sodium nitroprusside (SNP) induce a rapid decay of the thrombin-promoted increase of [Ca2+]i in aspirin-treated platelets incubated in the absence of external Ca2+. The mechanism of their effect was studied with a new method which utilizes ionomycin to increase [Ca2+]i, followed by bovine serum albumin (BSA) ... More
The von Willebrand factor-glycoprotein Ib/V/IX interaction induces actin polymerization and cytoskeletal reorganization in rolling platelets and glycoprotein Ib/V/IX-transfected cells.
AuthorsYuan Y, Kulkarni S, Ulsemer P, Cranmer SL, Yap CL, Nesbitt WS, Harper I, Mistry N, Dopheide SM, Hughan SC, Williamson D, de la Salle C, Salem HH, Lanza F, Jackson SP
JournalJ Biol Chem
PubMed ID10593912
Platelet adhesion to sites of vascular injury is initiated by the binding of the platelet glycoprotein (GP) Ib-V-IX complex to matrix-bound von Willebrand factor (vWf). This receptor-ligand interaction is characterized by a rapid on-off rate that enables efficient platelet tethering and rolling under conditions of rapid blood flow. We demonstrate ... More
Reactive oxygen species in essential hypertension and non-insulin-dependent diabetes mellitus.
AuthorsOrie NN, Zidek W, Tepel M
JournalAm J Hypertens
PubMed ID10619578
To evaluate whether increased levels of reactive oxygen species (ROS) are involved in the pathogenesis of essential hypertension (EH) and non-insulin-dependent diabetes mellitus (NIDDM), both resting and stimulated levels of intracellular ROS were measured in lymphocytes from patients with EH (n = 10), NIDDM (n = 16) and age-matched healthy ... More
Cortisol inhibition of calcium currents in guinea pig hippocampal CA1 neurons via G-protein-coupled activation of protein kinase C.
Authorsffrench-Mullen JM
JournalJ Neurosci
PubMed ID7823188
The inhibition of voltage-activated Ca2+ channel currents by cortisol (hydrocortisone), the principal glucocorticoid in man and guinea pig, was examined in freshly dissociated pyramidal neurons from the adult guinea pig hippocampal CA1 region using whole-cell voltage-clamp recordings. Steady-state inhibition by cortisol of the peak Ca2+ channel current evoked by depolarization ... More
The small Mr Ras-like GTPase Rap1 and the phospholipase C pathway act to regulate phagocytosis in Dictyostelium discoideum.
The function of the small-Mr Ras-like GTPase Rap1 remains largely unknown, but this protein has been demonstrated to regulate cortical actin-based morphologic changes in Dictyostelium and the oxidative burst in mammalian neutrophils. To test whether Rap1 regulates phagocytosis, we biochemically analyzed cell lines that conditionally and modestly overexpressed wild-type [Rap1 ... More
Glucose decreases Na+,K+-ATPase activity in pancreatic beta-cells. An effect mediated via Ca2+-independent phospholipase A2 and protein kinase C-dependent phosphorylation of the alpha-subunit.
AuthorsOwada S, Larsson O, Arkhammar P, Katz AI, Chibalin AV, Berggren PO, Bertorello AM
JournalJ Biol Chem
PubMed ID9890957
In the pancreatic beta-cell, glucose-induced membrane depolarization promotes opening of voltage-gated L-type Ca2+ channels, an increase in cytoplasmic free Ca2+ concentration ([Ca2+]i), and exocytosis of insulin. Inhibition of Na+,K+-ATPase activity by ouabain leads to beta-cell membrane depolarization and Ca2+ influx. Because glucose-induced beta-cell membrane depolarization cannot be attributed solely to ... More
Apoptotic membrane blebbing is regulated by myosin light chain phosphorylation.
AuthorsMills JC, Stone NL, Erhardt J, Pittman RN
JournalJ Cell Biol
PubMed ID9456322
The evolutionarily conserved execution phase of apoptosis is defined by characteristic changes occurring during the final stages of death; specifically cell shrinkage, dynamic membrane blebbing, condensation of chromatin, and DNA fragmentation. Mechanisms underlying these hallmark features of apoptosis have previously been elusive, largely because the execution phase is a rapid ... More
The bisindolylmaleimide GF 109203X is a potent and selective inhibitor of protein kinase C.
AuthorsToullec D, Pianetti P, Coste H, Bellevergue P, Grand-Perret T, Ajakane M, Baudet V, Boissin P, Boursier E, Loriolle F
JournalJ Biol Chem
PubMed ID1874734
Staurosporine is the most potent inhibitor of protein kinase C (PKC) described in the literature with a half-maximal inhibitory concentration (IC50) of 10 nM. Nevertheless, this natural product is poorly selective when assayed against other protein kinases. In order to obtain specific PKC inhibitors, a series of bisindolylmaleimides has been ... More