α2 Adrenergic Receptor Subtypes Expressed in Chinese Hamster Ovary Cells Activate Differentially Mitogen-activated Protein Kinase by a p21  Independent Pathway

Flordellis, Christos S.; Berguerand, Marie; Gouache, P.; Barbu, Véronique; Gavras, Haralambos; Handy, Diane E.; Béréziat, G.; Masliah, J.

doi:10.1074/jbc.270.8.3491

Cited by 46 publications

(40 citation statements)

References 32 publications

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“…6 and 7). Although we have not addressed the exact sequence of events, shear-dependent activations of ERK and JNK do involve similar signaling components including heterotrimeric G-proteins and tyrosine kinase(s) acting on Ras-dependent pathways as described by previous investigators in other G-protein-dependent ERK and JNK pathways (36,37,(47)(48)(49)(50)(51)(52).…”

Section: Figmentioning

confidence: 99%

“…Many examples of G-protein-dependent activation of ERK and JNK have been documented in other cell types. For example, ERK can be activated by G i -coupled receptor agonists, presumably by stimulating the release of ␤/␥-subunits of G i -proteins and subsequent activation of Ras-dependent or -independent cascades (47)(48)(49)(50)(51)(52). G␤/␥ and constituitively active mutants of ␣ 12 , ␣ 13 , and ␣ q have been shown to activate JNK through Ras and Rac-1-dependent pathways (24,34).…”

Section: Shear Stress Stimulates Jnk1 In a Time-and Thresholdmentioning

confidence: 99%

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Differential Effect of Shear Stress on Extracellular Signal-regulated Kinase and N-terminal Jun Kinase in Endothelial Cells

Sipos

et al. 1997

Journal of Biological Chemistry

251

261

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Shear stress differentially regulates production of many vasoactive factors at the level of gene expression in endothelial cells that may be mediated by mitogenactivated protein kinases, including extracellular signal-regulated kinase (ERK) and N-terminal Jun kinase (JNK). Here we show, using bovine aortic endothelial cells (BAEC), that shear stress differentially regulates ERK and JNK by mechanisms involving G i2 and pertussis toxin (PTx)-insensitive G-protein-dependent pathways, respectively. Shear activated ERK with a rapid, biphasic time course (maximum by 5 min and basal by 30-min shear exposure) and force dependence (minimum and maximum at 1 and 10 dyn/cm 2 shear stress, respectively). PTx treatment prevented shear-dependent activation of ERK1/2, consistent with a G i -dependent mechanism. In contrast, JNK activity was maximally turned on by a threshold level of shear force (0.5 dyn/ cm 2 or higher) with a much slower and prolonged time course (requiring at least 30 min to 4 h) than that of ERK. Also, PTx had no effect on shear-dependent activation of JNK. To further define the shear-sensitive ERK and JNK pathways, vectors expressing hemagglutinin epitope-tagged ERK (HA-ERK) or HA-JNK were cotransfected with other vectors by using adenoviruspolylysine in BAEC. Expression of the mutant ␣ i2 (G203), antisense G␣ i2 and a dominant negative Ras (N17Ras) prevented shear-dependent activation of HA-ERK, while that of ␣ i2 (G204) and antisense ␣ i3 did not. Expression of a G␤/␥ scavenger, the carboxyl terminus of ␤-adrenergic receptor kinase (␤ARK-ct), and N17Ras inhibited sheardependent activation of HA-JNK. Treatment of BAEC with genistein prevented shear-dependent activation of ERK and JNK, indicating the essential role of tyrosine kinase(s) in both ERK and JNK pathways. These results provide evidence that 1) G i2 -protein, Ras, and tyrosine kinase(s) are upstream regulators of shear-dependent activation of ERK and 2) that shear-dependent activation of JNK is regulated by mechanisms involving G␤/␥, Ras, and tyrosine kinase(s).Endothelial cells lining the inner vessel wall are in direct contact with flowing blood, which generates a frictional force, hemodynamic shear stress, acting on the surface of the endothelium. Hemodynamic shear stress controls vascular tone, vessel wall remodeling, interaction of blood cells with endothelium, coagulation, and fibrinolysis (1). The focal pattern of atherosclerotic lesions in areas of low and/or unstable shear stress further highlights the importance of shear stress in the atherogenic process (2, 3). Endothelial cells play a key role in shear-dependent vascular changes, sensing shear stress by an unidentified mechanoreceptor(s) followed by production of autocrine and paracrine factors (1). For example, hemodynamic shear stress selectively and differentially regulates production of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, platelet-derived growth factor-B, basic fibroblast growth factor, transforming growth factor ␤-1, tissue plasminogen activator,...

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Section: Figmentioning

confidence: 99%

Section: Shear Stress Stimulates Jnk1 In a Time-and Thresholdmentioning

confidence: 99%

Differential Effect of Shear Stress on Extracellular Signal-regulated Kinase and N-terminal Jun Kinase in Endothelial Cells

Sipos

et al. 1997

Journal of Biological Chemistry

251

261

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“…8) suggest that this is the case. Cooperative activation of MAPK by ␣ 2 -adrenergic agonists and PMA was recently reported in Chinese hamster ovary cells; the ␣ 2A -adrenergic response was Ras-independent (44). Two independent signals, one of which is PKC-dependent, are needed for maximal activation of MAPK by the G-protein-coupled anaphylatoxin C5a receptor (45).…”

Section: Fig 8 Effects Of Agonists On Tyrosine Phosphorylation Andmentioning

confidence: 99%

Synergistic Effects of Insulin and Phorbol Ester on Mitogen-activated Protein Kinase in Rat-1 HIR Cells

Knoepp

Wisehart-Johnson

Buse

et al. 1996

Journal of Biological Chemistry

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Regulation of the activity of the extracellular signal regulated kinase (ERK) mitogen-activated protein kinases was examined in Rat-1 HIR, a fibroblast cell line overexpressing the human insulin receptor. Insulin or phorbol ester induced partial activations of ERKs, while a combination of insulin and phorbol ester resulted in a synergistic activation. Preincubation with phorbol ester increased the subsequent response to insulin. Phorbol ester did not enhance tyrosine phosphorylation of the insulin receptor. Insulin did not enhance activation of phospholipase D in response to phorbol ester. Lysophosphatidic acid also acted synergistically with insulin to induce ERK activation. Lysophosphatidic acid alone had little effect on ERK, and did not activate phospholipase D. The combination of phorbol ester and insulin maintained tyrosine phosphorylation of focal adhesion kinase, while insulin alone decreased its tyrosine phosphorylation. Phorbol ester induced phosphorylation of Shc on serine/threonine, while insulin induced tyrosine phosphorylation of Shc and Shc-Grb2 binding. These results suggest that full activation of ERKs in fibroblasts can require the cooperation of at least two signaling pathways, one of which may result from a protein kinase C-dependent phosphorylation of effectors regulating ERK activation. In this manner, phorbol esters may enhance mitogenic signals initiated by growth factor receptors.The ERK 1 mitogen-activated protein kinases (MAPKs), which are activated in response to a wide variety of growth factors, hormones, and other mitogenic stimuli, have been linked to the induction of cell proliferation (1). The insulin receptor, a tyrosine kinase, can elicit both metabolic and mitogenic responses (2). The insulin receptor binds to several effectors, with binding to insulin receptor substrate-1 (IRS-1) mediating most of the metabolic effects of insulin. Mutation or deletion of some of the phosphorylatable tyrosines in the insulin receptor can enhance its mitogenic activity (3), suggesting that multifunctionality of the receptor may compromise its mitogenic potential. Phorbol ester tumor promoters can act additively or synergistically with insulin to induce mitogenesis (4, 5).The mitogenic activity of the insulin receptor has been correlated with its ability to activate MAPK, a response that is mediated predominantly through interaction of the insulin receptor with Shc (6). IRS-1 and Shc compete for binding to Grb2, such that IRS-1 may either inhibit (7) or enhance (8) activation of MAPK. Tyrosine-phosphorylated Shc binds to the adapter Grb2, causing disassembly of SOS from Grb2 resulting in GDP-GTP exchange on Ras (9). GTP-bound Ras promotes activation of Raf-1 kinase (1, 10). Raf-1 phosphorylates and activates MEK (mitogen-activated protein kinase kinase/ERK kinase), which phosphorylates and activates MAPK. One downstream effector of MAPK is RSK, another protein serine/threonine kinase. It is clear that the insulin receptor initiates signals that are independent of MAPK activation (reviewed in Ref...

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“…The CHO cells stably expressing the rat a 2B adrenergic receptor (CHO-2B cells) were maintained as described previously [25]. CHO-2B cells were stably transfected with either wild-type cPLA 2 /pcDNA3, myc-cPLA 2 /pcDNA3, Lck-cPLA 2 /pcDNA3 or cPLA 2 -Ras/pcDNA3 using the calcium phosphate precipitation method.…”

Section: Cell Culture Stable Transfection Of Cho-2b Cells Infectionmentioning

confidence: 99%

“…In CHO-2B cells it was possible to separately induce receptor-mediated phosphorylation and activation of cPLA 2 by Ca 2 [24]. Stimulation of the receptor with epinephrine causes pertussis toxin-sensitive, Ras-independent activation of mitogen-activated protein kinase (MAP kinase; [25]), leading to cPLA 2 phosphorylation [24,26], but has only a modest effect on the release of D 4 Ach [24]. Free D 4 Ach is maximally produced by stimulating the cells with both epinephrine and the Ca 2+ ionophore A23187, which results in a massive entry of extracellular Ca 2+ [24].…”

mentioning

confidence: 99%

N‐terminal and C‐terminal plasma membrane anchoring modulate differently agonist‐induced activation of cytosolic phospholipase A₂

Klapisz

Ziari

Wendum

et al. 1999

European Journal of Biochemistry

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The 85 kDa cytosolic phospholipase A 2 (cPLA 2 ) plays a key role in liberating arachidonic acid from the sn-2 position of membrane phospholipids. When activated by extracellular stimuli, cPLA 2 undergoes calciumdependent translocation from cytosol to membrane sites which are still a matter of debate. In order to evaluate the effect of plasma membrane association on cPLA 2 activation, we constructed chimeras of cPLA 2 constitutively targeted to the plasma membrane by the N-terminal targeting sequence of the protein tyrosine kinase Lck (Lck-cPLA 2 ) or the C-terminal targeting signal of K-Ras4B (cPLA 2 -Ras). Constitutive expression of these chimeras in Chinese hamster ovary cells overproducing the a 2B adrenergic receptor (CHO-2B cells) did not affect the basal release of [ 3 H]arachidonic acid, indicating that constitutive association of cPLA 2 with cellular membranes did not ensure the hydrolysis of membrane phospholipids. However, Lck-cPLA 2 increased [ 3 H]arachidonic acid release in response to receptor stimulation and to increased intracellular calcium, whereas cPLA 2 -Ras inhibited it, compared with parental CHO-2B cells and CHO-2B cells producing comparable amounts of recombinant wild-type cPLA 2 . The lack of stimulation of cPLA 2 -Ras was not due to a decreased enzymatic activity as measured using an exogenous substrate, or to a decreased phosphorylation of the protein. These results show that the plasma membrane is a suitable site for cPLA2 activation when orientated correctly.

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α2 Adrenergic Receptor Subtypes Expressed in Chinese Hamster Ovary Cells Activate Differentially Mitogen-activated Protein Kinase by a p21 Independent Pathway

Cited by 46 publications

References 32 publications

Differential Effect of Shear Stress on Extracellular Signal-regulated Kinase and N-terminal Jun Kinase in Endothelial Cells

Differential Effect of Shear Stress on Extracellular Signal-regulated Kinase and N-terminal Jun Kinase in Endothelial Cells

Synergistic Effects of Insulin and Phorbol Ester on Mitogen-activated Protein Kinase in Rat-1 HIR Cells

N‐terminal and C‐terminal plasma membrane anchoring modulate differently agonist‐induced activation of cytosolic phospholipase A₂

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α2 Adrenergic Receptor Subtypes Expressed in Chinese Hamster Ovary Cells Activate Differentially Mitogen-activated Protein Kinase by a p21 Independent Pathway

Cited by 46 publications

References 32 publications

Differential Effect of Shear Stress on Extracellular Signal-regulated Kinase and N-terminal Jun Kinase in Endothelial Cells

Differential Effect of Shear Stress on Extracellular Signal-regulated Kinase and N-terminal Jun Kinase in Endothelial Cells

Synergistic Effects of Insulin and Phorbol Ester on Mitogen-activated Protein Kinase in Rat-1 HIR Cells

N‐terminal and C‐terminal plasma membrane anchoring modulate differently agonist‐induced activation of cytosolic phospholipase A2

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Product

Resources

About

N‐terminal and C‐terminal plasma membrane anchoring modulate differently agonist‐induced activation of cytosolic phospholipase A₂