Role of MAP kinase activation in Nramp1 mRNA stability in RAW264.7 macrophages expressing Nramp1Gly169

Many receptor-linked agents that prime or activate the NADPH oxidase in polymorphonuclear neutrophils (PMNs) elicit changes in cytosolic Ca2+concentration and activate mitogen-activated protein (MAP) kinases. To investigate the role of Ca2+in the activation of p38 and p42/44 MAP kinases, we examined the effects of the Ca2+-selective ionophore ionomycin on priming and activation of the PMN oxidase. Ionomycin caused a rapid rise in cytosolic Ca2+that was due to both a release of cytosolic Ca2+stores and Ca2+influx. Ionomycin also activated (2 μM) and primed (20–200 nM) the PMN oxidase. Dual phosphorylation of p38 MAP kinase and phosphorylation of its substrate activating transcription factor-2 were detected at ionomycin concentrations that prime or activate the PMN oxidase, while dual phosphorylation of p42/44 MAP kinase and phosphorylation of its substrate Elk-1 were elicited at 0.2–2 μM. SB-203580, a p38 MAP kinase antagonist, inhibited ionomycin-induced activation of the oxidase (68 ± 8%, P < 0.05) and tyrosine phosphorylation of 105- and 72-kDa proteins; conversely, PD-98059, an inhibitor of MAP/extracellular signal-related kinase 1, had no effect. Treatment of PMNs with thapsigargin resulted in priming of the oxidase and activation of p38 MAP kinase. Chelation of cytosolic but not extracellular Ca2+completely inhibited ionomycin activation of p38 MAP kinase, whereas chelation of extracellular Ca2+abrogated activation of p42/44 MAP kinase. These results demonstrate the importance of changes in cytosolic Ca2+for MAP kinase activation in PMNs.

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Role of the EGFR/Ras/Raf pathway in specification of photoreceptor cells in the Drosophila retina

Development ◽

10.1242/dev.128.7.1183 ◽

2001 ◽

Vol 128 (7) ◽

pp. 1183-1191 ◽

Cited By ~ 3

Author(s):

L. Yang ◽

N.E. Baker

Keyword(s):

Map Kinase ◽

Egf Receptor ◽

Eye Development ◽

Photoreceptor Cells ◽

Cell Types ◽

Cell Specification ◽

Kinase Activation ◽

Cell Spacing ◽

Egfr Activation

The Drosophila EGF receptor is required for differentiation of many cell types during eye development. We have used mosaic analysis with definitive null mutations to analyze the effects of complete absence of EGFR, Ras or Raf proteins during eye development. The Egfr, ras and raf genes are each found to be essential for recruitment of R1-R7 cells. In addition Egfr is autonomously required for MAP kinase activation. EGFR is not essential for R8 cell specification, either alone or redundantly with any other receptor that acts through Ras or Raf, or by activating MAP kinase. As with Egfr, loss of ras or raf perturbs the spacing and arrangement of R8 precursor cells. R8 cell spacing is not affected by loss of argos in posteriorly juxtaposed cells, which rules out a model in which EGFR acts through argos expression to position R8 specification in register between adjacent columns of ommatidia. The R8 spacing role of the EGFR was partially affected by simultaneous deletion of spitz and vein, two ligand genes, but the data suggest that EGFR activation independent of spitz and vein is also involved. The results prove that R8 photoreceptors are specified and positioned by distinct mechanisms from photoreceptors R1-R7.

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Interaction between Drosophila EGF receptor and vnd determines three dorsoventral domains of the neuroectoderm

Development ◽

10.1242/dev.125.18.3625 ◽

1998 ◽

Vol 125 (18) ◽

pp. 3625-3633 ◽

Cited By ~ 5

Author(s):

Y. Yagi ◽

T. Suzuki ◽

S. Hayashi

Keyword(s):

Map Kinase ◽

Receptor Tyrosine Kinase ◽

Egf Receptor ◽

Regulatory Region ◽

Homeobox Gene ◽

Kinase Activation ◽

Intermediate Column ◽

Kinase Signaling Pathway ◽

Map Kinase Signaling Pathway

Neurogenesis in Drosophila melanogaster starts by an ordered appearance of neuroblasts arranged in three columns (medial, intermediate and lateral) in each side of the neuroectoderm. Here we show that, in the intermediate column, the receptor tyrosine kinase DER represses expression of proneural genes, achaete and scute, and is required for the formation of neuroblasts. Most of the early function of DER is likely to be mediated by the Ras-MAP kinase signaling pathway, which is activated in the intermediate column, since a loss of a component of this pathway leads to a phenotype identical to that in DER mutants. MAP-kinase activation was also observed in the medial column where esg and proneural gene expression is unaffected by DER. We found that the homeobox gene vnd is required for the expression of esg and scute in the medial column, and show that vnd acts through the negative regulatory region of the esg enhancer that mediates the DER signal, suggesting the role of vnd is to counteract DER-dependent repression. Thus nested expression of vnd and the DER activator rhomboid is crucial to subdivide the neuroectoderm into the three dorsoventral domains.

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The role of p38 MAP kinase in the regulation of mRNA stability.

10.1349/ddlp.3030 ◽

2001 ◽

Author(s):

John Edward Connolly

Keyword(s):

Map Kinase ◽

Mrna Stability ◽

P38 Map Kinase

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Activation of mitogen-activated protein kinase and p70S6 kinase is not correlated with cerebellar granule cell survival

Biochemical Journal ◽

10.1042/bj3240365 ◽

1997 ◽

Vol 324 (2) ◽

pp. 365-369 ◽

Cited By ~ 42

Author(s):

Frank J. GUNN-MOORE ◽

Alan G. WILLIAMS ◽

Nicholas J. TOMS ◽

Jeremy M. TAVARÉ

Keyword(s):

Map Kinase ◽

Granule Cells ◽

Cerebellar Granule Cells ◽

Mitogen Activated Protein Kinase ◽

Kinase Activation ◽

Cerebellar Granule ◽

P70s6 Kinase ◽

Mitogen Activated Protein ◽

Sustained Activation

We have investigated the role of mitogen-activated protein (MAP) kinase in the survival of cerebellar granule cells in primary culture. Brain-derived neurotrophic factor (BDNF) and insulin, but not epidermal growth factor (EGF), promoted the survival of P6 cerebellar granule neurons. BDNF promoted a sustained activation of MAP kinase, whereas that induced by EGF was only transient. Insulin promoted a small but transient activation of MAP kinase that was completely blocked by PD98059, an inhibitor of MAP kinase kinase activation. PD98059 had no effect on the insulin- or BDNF-induced survival of cerebellar granule cells. We also investigated the role of p70S6 kinase in survival. The activation of p70S6 kinase by EGF was transient, whereas BDNF and insulin promoted a sustained activation of p70S6 kinase. Rapamycin, which blocked p70S6 kinase activation, had no effect on the BDNF- or insulin-induced survival of cerebellar granule cells. We conclude that sustained activation of MAP kinase is not correlated with the survival response of cerebellar granule cells; indeed insulin-mediated survival is independent of MAP kinase. Survival of cerebellar granule cells is also independent of the activation of p70S6 kinase.

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A role for MAP kinase in differentiated smooth muscle contraction evoked by α-adrenoceptor stimulation

AJP Cell Physiology ◽

10.1152/ajpcell.1998.275.4.c1081 ◽

1998 ◽

Vol 275 (4) ◽

pp. C1081-C1086 ◽

Cited By ~ 125

Author(s):

Chantal Dessy ◽

Inkyeom Kim ◽

Carrie L. Sougnez ◽

Regent Laporte ◽

Kathleen G. Morgan

Keyword(s):

Smooth Muscle ◽

Muscle Contraction ◽

Map Kinase ◽

Specific Inhibitor ◽

Smooth Muscle Contraction ◽

Isometric Tension ◽

Kinase Activation ◽

Protein Map ◽

Mitogen Activated Protein

The purpose of this study was to investigate the potential role of mitogen-activated protein (MAP) kinase in smooth muscle contraction by monitoring MAP kinase activation, caldesmon phosphorylation, and contractile force during agonist stimulation. Isometric tension in response to KCl and phenylephrine (PE) was measured from strips of ferret aorta. MAP kinase activation was monitored by Western blot using a phosphospecific p44/p42 MAP kinase antibody. Caldesmon phosphorylation was assessed using specific phosphocaldesmon antibodies. We report here that treatment of smooth muscle strips with PD-098059, a specific inhibitor of MAP kinase kinase, did not detectably modify the KCl-evoked contraction but significantly inhibited the contraction to PE in the absence of extracellular Ca2+. In this experimental condition, where the contraction occurs in the absence of increases in 20-kDa myosin light chain phosphorylation, PD-098059 also inhibited significantly MAP kinase and caldesmon phosphorylation. Collectively, these results demonstrate a direct cause-and-effect relationship between MAP kinase activation and Ca2+-independent smooth muscle contraction and support the concept of caldesmon phosphorylation as the missing link between both events.

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Role of CaMKII in nicotine-induced p38 map kinase activation

Nitric Oxide ◽

10.1016/j.niox.2012.04.040 ◽

2012 ◽

Vol 27 ◽

pp. S11

Author(s):

Aya Kajiwara ◽

Yukihiro Tsuchiya ◽

Hideshi Ihara ◽

Yasuo Watanabe

Keyword(s):

Map Kinase ◽

P38 Map Kinase ◽

Kinase Activation

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Interleukin-2 triggers a novel phosphatidylinositol 3-kinase-dependent MEK activation pathway.

Molecular and Cellular Biology ◽

10.1128/mcb.15.6.3049 ◽

1995 ◽

Vol 15 (6) ◽

pp. 3049-3057 ◽

Cited By ~ 100

Author(s):

L M Karnitz ◽

L A Burns ◽

S L Sutor ◽

J Blenis ◽

R T Abraham

Keyword(s):

Map Kinase ◽

Interleukin 2 ◽

Phosphatidylinositol 3 Kinase ◽

Lipid Kinase ◽

Kinase Activation ◽

Activation Pathway ◽

Drug Concentrations ◽

Phase Entry ◽

Phosphatidylinositol 3

Phosphatidylinositol 3-kinase (PI3-K) has been implicated as a signal-transducing component in interleukin-2 (IL-2)-induced mitogenesis. However, the function of this lipid kinase in regulating IL-2-triggered downstream events has remained obscure. Using the potent and specific PI3-K inhibitor, wortmannin, we assessed the role of PI3-K in IL-2-mediated signaling and proliferation in the murine T-cell line CTLL-2. Addition of the drug to exponentially growing cells resulted in an accumulation of cells in the G0/G1 phase of the cell cycle. Furthermore, wortmannin also partially suppressed IL-2-induced S-phase entry in G1-synchronized cells. Analysis of IL-2-triggered signaling pathways revealed that wortmannin pretreatment resulted in complete inhibition of IL-2-provoked p70 S6 kinase activation and also attenuated IL-2-induced MAP kinase activation at drug concentrations identical to those required for inhibition of PI3-K catalytic activity. Wortmannin also diminished the IL-2-triggered activation of the MAP kinase activator, MEK, but did not inhibit activation of Raf, the canonical upstream activator of MEK. These results suggest that a novel wortmannin-sensitive activation pathway regulates MEK and MAP kinase in IL-2-stimulated T lymphocytes.

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