Parietal cell MAP kinases: multiple activation pathways

Nakamura, Kyotaro; Zhou, Cheng-Jing; Parente, John A.; Chew, Catherine S.

doi:10.1152/ajpgi.1996.271.4.g640

Cited by 27 publications

(24 citation statements)

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“…While several studies have found that wortmannin (10 -15) or dominantnegative PI 3-kinase (9) effectively inhibits activation of the MAP kinase cascade, many other studies have found that inhibition of PI 3-kinase has no effect on the activation of Erk proteins (17)(18)(19). The results in Fig.…”

Section: Discussionmentioning

confidence: 84%

Section: Pimentioning

confidence: 99%

“…A recent study found that overexpression of the p110␥ type of PI 3-kinase resulted in the activation of Erk, but that p110␣ did not (9). Inhibition of PI 3-kinase with wortmannin (10 -16) or dominant-negative PI 3-kinase (9) has been shown to block activation of MAP kinase in some but not all cells (17)(18)(19).Several direct targets of the lipid products of PI 3-kinase have been identified that could act as intermediates between PI 3-kinase and the MAP kinase pathway. Members of the novel PKC family (calcium-independent), PKC⑀, PKC␦, and PKC (20), have been shown to be activated in vitro by two lipid products of PI 3-kinase, PtdIns-3,4-P 2 and PtdIns-3,4,5-P 3 .…”

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confidence: 99%

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Conditional Inhibition of the Mitogen-activated Protein Kinase Cascade by Wortmannin

Duckworth

Cantley

1997

Journal of Biological Chemistry

183

150

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Phosphoinositide (PI) 3-kinase and the mitogen-activated protein (MAP) kinase cascades are activated by many of the same ligands. Several groups have reported involvement of PI 3-kinase in the activation of Erk1 and Erk2, whereas many other groups have shown that activation of Erk1 and Erk2 is not sensitive to inhibitors of PI 3-kinase such as wortmannin. Here we show that wortmannin inhibition of the MAP kinase pathway is cell type-and ligand-specific. Wortmannin blocks platelet-derived growth factor (PDGF)-dependent activation of Raf-1 and the MAP kinase cascade in Chinese hamster ovary cells, which have few PDGF receptors, but has no significant effect on Erk activation in Swiss 3T3 cells, which have high levels of PDGF receptors. However, wortmannin blocks activation of Erk proteins if Swiss 3T3 cells are stimulated with lower, physiological levels of PDGF. These results suggest that PI 3-kinase is in an efficient pathway for activation of MAP kinase, but that MAP kinase can be stimulated by a redundant pathway when a large number of receptors are activated. We present evidence that a protein kinase C family member downstream of phospholipase C␥ is involved in the redundant pathway. PI1 3-kinase has been implicated as being involved in the signal transduction of virtually all growth factors studied and in the transformation of cells by several oncoproteins (1, 2). Activation of PI 3-kinase with growth factors results in the appearance of the lipid products of this enzyme, PtdIns-3,4-P 2 and PtdIns-3,4,5-P 3 , within seconds to minutes. There is also a correlation between the elevation in PtdIns-3,4-P 2 and PtdIns-3,4,5-P 3 levels and cell transformation. These correlations have suggested an important role for PI 3-kinase in signal transduction pathways leading to cell growth and transformation. Indeed, the catalytic subunit of PI 3-kinase (p110␣) has recently been identified as a retroviral oncogene (3). Overexpression of p110␣ in chick embryo fibroblasts results in constitutive elevation of PtdIns-3,4-P 2 and PtdIns-3,4,5-P 3 and cell transformation.The MAP kinase pathway is another key component in the transduction of signals leading to growth and transformation. This pathway consists of a linear cascade of the protein kinases Raf, MEK, and MAP kinase/Erk; like PI 3-kinase, Erk1 and Erk2 are acutely activated by growth factors and are found constitutively activated in many transformed cell lines. The Erk proteins are phosphorylated and activated by the dual specificity kinase MEK (MAP kinase/Erk kinase), which is phosphorylated and activated by the serine/threonine kinase Raf. Raf is recruited to the membrane of activated cells by direct binding to Ras-GTP. This recruitment by activated Ras is necessary but not sufficient for full activation of Raf (4); therefore, other factors that are necessary for activation of the MAP kinase pathway may feed into the pathway at Raf. A search for other sources that feed into the MAP kinase pathway has yielded several candidates including Src, members of the PKC family, ...

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Section: Discussionmentioning

confidence: 84%

Section: Pimentioning

confidence: 99%

mentioning

confidence: 99%

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Conditional Inhibition of the Mitogen-activated Protein Kinase Cascade by Wortmannin

Duckworth

Cantley

1997

Journal of Biological Chemistry

183

150

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“…For example, overexpression of a constitutively active p110-␣, a PI3-K isoform, has been shown to activate the Ras-ERK pathway in at least one system (31), but not in others (22,37,42,47). In addition, many studies have demonstrated a requirement of PI3-K activity for ERK activation by multiple diverse stimuli (13,16,17,25,40,47,76,86,89,91), while other reports failed to show a sensitivity of some of these same stimuli to PI3-K inhibitors (59,78,85,92). One explanation for these apparent discrepancies may be that the ability of PI3-K inhibitors to block ERK activation is dependent on the cell type, type of stimuli, and strength of the signal (17,100).…”

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confidence: 99%

Role of Phosphoinositide 3-Kinase and Endocytosis in Nerve Growth Factor-Induced Extracellular Signal-Regulated Kinase Activation via Ras and Rap1

York

Molliver

Grewal

et al. 2000

Molecular and Cellular Biology

215

124

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Neurotrophins promote multiple actions on neuronal cells including cell survival and differentiation. The best-studied neurotrophin, nerve growth factor (NGF), is a major survival factor in sympathetic and sensory neurons and promotes differentiation in a well-studied model system, PC12 cells. To mediate these actions, NGF binds to the TrkA receptor to trigger intracellular signaling cascades. Two kinases whose activities mediate these processes include the mitogen-activated protein (MAP) kinase (or extracellular signal-regulated kinase [ERK]) and phosphoinositide 3-kinase (PI3-K). To examine potential interactions between the ERK and PI3-K pathways, we studied the requirement of PI3-K for NGF activation of the ERK signaling cascade in dorsal root ganglion cells and PC12 cells. We show that PI3-K is required for TrkA internalization and participates in NGF signaling to ERKs via distinct actions on the small G proteins Ras and Rap1. In PC12 cells, NGF activates Ras and Rap1 to elicit the rapid and sustained activation of ERKs respectively. We show here that Rap1 activation requires both TrkA internalization and PI3-K, whereas Ras activation requires neither TrkA internalization nor PI3-K. Both inhibitors of PI3-K and inhibitors of endocytosis prevent GTP loading of Rap1 and block sustained ERK activation by NGF. PI3-K and endocytosis may also regulate ERK signaling at a second site downstream of Ras, since both rapid ERK activation and the Ras-dependent activation of the MAP kinase kinase kinase B-Raf are blocked by inhibition of either PI3-K or endocytosis. The results of this study suggest that PI3-K may be required for the signals initiated by TrkA internalization and demonstrate that specific endocytic events may distinguish ERK signaling via Rap1 and Ras.Neurotrophins have long been recognized for their role in regulating neuronal survival, cell growth, differentiation, and neuronal plasticity. The archetypal neurotrophin, nerve growth factor (NGF), elicits most of these effects by binding and activating the receptor tyrosine kinase (RTK), TrkA, which leads to the activation of several well-defined signaling cascades. Of these, the phosphoinositide 3-kinase (PI3-K) and extracellular signal-regulated kinase (ERK) pathways are two of the most extensively studied. PI3-Ks have been implicated in multiple biological responses including membrane trafficking, proliferation, differentiation, and survival (67). These kinases consist of a family of proteins which phosphorylate phosphatidylinositol (PI) at the D3 position and have been categorized into three classes based on their lipid substrate specificity in vitro (96). The lipid products of PI3-Ks {PI 3-phosphate [PI(3)P], PI(3,4)P, PI(3,5)P, and PI(3,4,5)P} are known to act as second messengers and mediate most of the known functions of PI3-Ks in cells (45).The mitogen-activated protein kinase family members, ERK1 and ERK2, can also be activated by a wide variety of stimuli to promote a diverse array of cellular functions (77). In addition to their established rol...

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“…In particular, we and others have shown that carbachol induces the ERKs (36,47,48), the c-Jun NH 2 -terminal kinases (JNKs) (35), and p38 kinase (37), molecules known to regulate multiple important physiological functions in the parietal cells. Whereas the ERKs and p38 kinase appear to be involved in the process of gastric acid production (37,48), activation of the JNKs seems to be an important step in the response of the parietal cells to stress and inflammation (35).…”

Section: Discussionmentioning

confidence: 99%

Regulation and function of COX-2 gene expression in isolated gastric parietal cells

Pausawasdi

Ramamoorthy

Crofford

et al. 2002

American Journal of Physiology-Gastrointestinal and Liver Physi

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We examined expression, function, and regulation of the cyclooxygenase (COX)-2 gene in gastric parietal cells. COX-2-specific mRNA was isolated from purified (>95%) canine gastric parietal cells in primary culture and measured by Northern blots using a human COX-2 cDNA probe. Carbachol was the most potent inducer of COX-2 gene expression. Gastrin and histamine exhibited minor stimulatory effects. Carbachol-stimulated expression was inhibited by intracellular Ca2+chelator 1,2-bis(2-aminophenoxy)ethane- N,N,N′,N′-tetraacetic acid-AM (90%), protein kinase C (PKC) inhibitor GF-109203X (48%), and p38 kinase inhibitor SB-203580 (48%). Nuclear factor (NF)-κB inhibitor 1-pyrrolidinecarbodithioic acid inhibited carbachol-stimulated expression by 80%. Similar results were observed in the presence of adenoviral vector Ad.dom.neg.IκB, which expresses a repressor of NF-κB. Addition of SB-203580 with Ad.dom.neg.IκB almost completely blocked carbachol stimulation of COX-2 gene expression. We examined the effect of carbachol on PGE2release by enzyme-linked immunoassay. Carbachol induced PGE2 release. Ad.dom.neg.IκB, alone or with SB-203580, produced, respectively, partial (70%) and almost complete (>80%) inhibition of carbachol-stimulated PGE2 production. Selective COX-2 inhibitor NS-398 blocked carbachol-stimulated PGE2 release without affecting basal PGE2production. In contrast, indomethacin inhibited both basal and carbachol-stimulated PGE2 release. Carbachol induces COX-2 gene expression in the parietal cells through signaling pathways that involve intracellular Ca2+, PKC, p38 kinase, and activation of NF-κB. The functional significance of these effects seems to be stimulation of PGE2 release.

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Parietal cell MAP kinases: multiple activation pathways

Cited by 27 publications

References 0 publications

Conditional Inhibition of the Mitogen-activated Protein Kinase Cascade by Wortmannin

Conditional Inhibition of the Mitogen-activated Protein Kinase Cascade by Wortmannin

Role of Phosphoinositide 3-Kinase and Endocytosis in Nerve Growth Factor-Induced Extracellular Signal-Regulated Kinase Activation via Ras and Rap1

Regulation and function of COX-2 gene expression in isolated gastric parietal cells

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