Phosphorylation of p42/44MAPK by Various Signal Transduction Pathways Activates Cytosolic Phospholipase A2to Variable Degrees

Rossum, Gerda S.A.T. van; Klooster, Rinse; Bosch, H. van den; Verkleij, Arie J.; Boonstra, Johannes

doi:10.1074/jbc.m101361200

Cited by 28 publications

(14 citation statements)

References 69 publications

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“…We previously reported that PAF synthesis mediated by VEGF-A 165 requires the activation of sPLA 2 as opposed to cPLA 2 . However, because it is well established that p42/44 MAPK can promote the phosphorylation of cPLA 2 (8,46) and that p42/44 MAPK activation is essential for PAF synthesis (20), we assessed the contribution of both PLA 2 on PGI 2 synthesis. The blockade of cPLA 2 prevented completely the synthesis of PGI 2 , whereas the inhibition of sPLA 2 induced a non-significant decrease of PGI 2 synthesis.…”

Section: Discussionmentioning

confidence: 99%

Vascular Endothelial Growth Factor (VEGF)-A165-induced Prostacyclin Synthesis Requires the Activation of VEGF Receptor-1 and -2 Heterodimer

Neagoe

Lemieux

Sirois

2005

Journal of Biological Chemistry

113

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We previously reported that vascular endothelial growth factor (VEGF)-A 165 inflammatory effect is mediated by acute platelet-activating factor synthesis from endothelial cells upon the activation of VEGF receptor-2 (VEGFR-2) and its coreceptor, neuropilin-1 (NRP-1). In addition, VEGF-A 165 promotes the release of other endothelial mediators including nitric oxide and prostacyclin (PGI 2 ). However, it is unknown whether VEGF-A 165 is mediating PGI 2 synthesis through VEGF receptor-1 (VEGFR-1) and/or VEGF receptor-2 (VEGFR-2) activation and whether the coreceptor NRP-1 potentiates VEGF-A 165 activity. In this study, PGI 2 synthesis in bovine aortic endothelial cells (BAEC) was assessed by quantifying its stable metabolite (6-keto prostaglandin F 1␣ , 6-keto PGF 1␣

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Section: Discussionmentioning

confidence: 99%

Vascular Endothelial Growth Factor (VEGF)-A165-induced Prostacyclin Synthesis Requires the Activation of VEGF Receptor-1 and -2 Heterodimer

Neagoe

Lemieux

Sirois

2005

Journal of Biological Chemistry

113

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“…The mechanism by which Ras mediates these effects is believed to be through a direct interaction with downstream effectors resulting in a persistent activation of MAP kinase signaling pathways (39 -41). It is well established that one characteristic of transformed cells is perturbation of lipid synthetic and degradative pathways (71)(72)(73), suggesting an active role of lipids in oncogenic transformation. Expression of oncogenic Ras correlates with increased levels of phosphocholine and phosphoethanolamine (45,(73)(74)(75), diacylglycerols (76), inositol phosphates (77), and arachidonic acid (78).…”

Section: Transient Expression Of Sp3 Increases the Amount Of Both Ct␣mentioning

confidence: 99%

Oncogenic Ha-Ras Transformation Modulates the Transcription of the CTP:Phosphocholine Cytidylyltransferase α Gene via p42/44MAPK and Transcription Factor Sp3

Bakovic¹,

Waite²,

Vance

2003

Journal of Biological Chemistry

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Phosphatidylcholine (PC)1 is the most abundant phospholipid in mammalian cellular membranes. Besides having a structural role in membranes and lipoproteins (1-3), PC plays an important role in signal transduction as a source of lipid second messengers (1-3). In all nucleated cells, PC is made primarily through the CDP-choline pathway in which the key enzyme is CTP:phosphocholine cytidylyltransferase (CT) (2-6).Two genes that encode CT activity have been identified and characterized. CT␣ is expressed in many cells and tissues (7-13) and has a predicted structure that contains catalytic, phosphorylation, and lipid binding domains as well as a nuclear localization sequence (8, 14 -21). Recently, CT␤ has been identified in human tissues and appears to exist as two splice variants, CT␤1 and CT␤2, differing at their C termini (22, 23). Like CT␣, CT␤1/2 contains catalytic and lipid binding domains. However, CT␤1 lacks the phosphorylation domain, and both CT␤1 and CT␤2 lack the nuclear localization sequence (23).In the last several years, studies have shown that CT can be regulated at both the transcriptional level and post-transcriptionally. CT mRNA is increased after partial hepatectomy in rats (13), after stimulation with colony-stimulating factor 1 in macrophages (24), and during development and growth (25)(26)(27)(28). It remains to be determined whether these increases in the message levels are the result of CT␣ and/or CT␤1/2 mRNA stability, an increase in gene transcription, or a combination of both.The murine CT␣ gene (Ctpct) was cloned and characterized by Tang and co-workers (29). The Ctpct promoter contains several putative elements for binding transcription factors, including Ap1, an overlapping site for nuclear factor-B, E2F, and Elk1, one sterol response element, as well as three elements for Sp-related factors (30). We have shown that Sp1, Sp2, and Sp3 bind competitively to three GC-rich elements and that relative promoter activity depends upon the abundance of these factors (31). We further established that transcription enhancer factor-4 can bind to an upstream regulatory element (Ϫ103/Ϫ82) and enhance the CT␣ gene expression through its interactions with the basal transcriptional machinery (32). In agreement with the finding that lipoprotein deficiency induces the expression of CT␣ mRNA and protein in alveolar type II epithelial cells (33), and our observation that the CT␣ promoter contains a putative sterol response element (30), studies by Kast et al. (34) indicate a role for cholesterol/sterol response element-binding protein and the functionality of the sterol response element in the regulation of CT␣ gene expression in Chinese hamster ovary cells and THP-1 cells. On the other hand, Lagace et al. (35) have shown that cholesterol/sterol response element-binding protein can stimulate PC biosynthe-

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“…U-0126 prevents ERK activation downstream of MEK (43) and is a more complete blocker of ERK activation than the commonly used PD-98059. We found that U-0126 almost completely blocked LPS-induced TNF in adherence and low-adherence conditions (Fig.…”

Section: Erk Activation Is Linked To Lps-induced Tnf Productionmentioning

confidence: 99%

Interaction of matrix with integrin receptors is required for optimal LPS-induced MAP kinase activation

Monick

Powers

Butler

et al. 2002

American Journal of Physiology-Lung Cellular and Molecular Phys

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Exposure of macrophages to endotoxin [lipopolysaccharide (LPS)] results in a cascade of events resulting in the release of multiple inflammatory and anti-inflammatory mediators. The Toll-like receptor (TLR) 4 complex is the major receptor that mediates LPS signaling. However, there is evidence that other surface molecules may play a complementary role in the TLR-induced events. Integrin receptors are one class of receptors that have been linked to LPS signaling. This study investigates the role of macrophage integrin receptors in the activation of mitogen-activated protein (MAP) kinases by LPS. In conditions where macrophages were not permitted to adhere to matrix or a tissue culture surface, we found a decrease in LPS signaling as documented by a marked reduction in tyrosine phosphorylation of whole cell proteins. This was accompanied by a significant decrease in extracellular signal-regulated kinase and c-Jun NH 2-terminal kinase MAP kinase activation. Inhibition of integrin signaling, with EDTA or RGD peptides, decreased LPS-induced MAP kinase activity. The functional consequence of blocking integrin signaling was demonstrated by decreased LPS-induced tumor necrosis factor-␣ production. These observations demonstrate that, in addition to the TLR receptor complex, optimal LPS signaling requires complementary signals from integrin receptors.Toll-like receptor; tumor necrosis factor; integrins; lipopolysaccharide; mitogen-activated protein LIPOPOLYSACCHARIDE (LPS) plays a pivotal role in the innate immune response to gram-negative bacteria (31, 42). LPS signaling is initiated by an interaction between LPS and LPS-binding protein, allowing binding to CD14 and association with another cell membrane receptor, which contains an intracellular signaling domain. This other receptor has recently been determined to be Toll-like receptor (TLR) 4, and significant work has been done to define this complex (for review see Refs. 1,17,22). In addition to the TLR complex, a number of other membrane receptors have been proposed to play a role in LPS signaling. These include ␤ 2 -integrins, a purinergic receptor (P2X 7 ), moesin, triggering receptor expressed on myeloid cells-1, a recently described complex that includes heat shock proteins 90 and 70, complement receptor 4, and bone morphogenic protein (20,23,28,40,41). Several previous studies have suggested a role for the integrin receptors in LPS signaling (12,23,29,36). Recently, Perera et al. (29) showed a decreased LPS response [some cytokines, e.g., cyclooxygenase-2 and interleukin (IL)-12 p35, and a slight decrease in p38 activation] in peritoneal macrophages from CD11b (a major integrin chain in macrophages)-knockout mice (29). This study evaluates the link between adherence and LPS-induced mitogen-activated protein (MAP) kinase activation and tumor necrosis factor (TNF)-␣ production in a murine macrophage line.Integrins are a family of cell surface glycoproteins (for review see Refs. 2,3,18). Each integrin is a heterodimer that contains an ␣-and a ␤-subunit. Each subuni...

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Phosphorylation of p42/44MAPK by Various Signal Transduction Pathways Activates Cytosolic Phospholipase A2to Variable Degrees

Abstract: Arachidonic acid has been implicated to play a role in physiological and pathophysiological processes and is selectively released by the 85-kDa cytosolic phospholipase A 2 (cPLA 2 ).

Cited by 28 publications

References 69 publications

Vascular Endothelial Growth Factor (VEGF)-A165-induced Prostacyclin Synthesis Requires the Activation of VEGF Receptor-1 and -2 Heterodimer

Vascular Endothelial Growth Factor (VEGF)-A165-induced Prostacyclin Synthesis Requires the Activation of VEGF Receptor-1 and -2 Heterodimer

Oncogenic Ha-Ras Transformation Modulates the Transcription of the CTP:Phosphocholine Cytidylyltransferase α Gene via p42/44MAPK and Transcription Factor Sp3

Interaction of matrix with integrin receptors is required for optimal LPS-induced MAP kinase activation

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