Platelet-derived-growth-factor stimulation of the p42/p44 mitogen-activated protein kinase pathway in airway smooth muscle: role of pertussis-toxin-sensitive G-proteins, c-Src tyrosine kinases and phosphoinositide 3-kinase

Conway, Ann-Marie; Rakhit, Soma; Pyne, Susan; Pyne, Nigel J.

doi:10.1042/bj3370171

Cited by 86 publications

(37 citation statements)

References 17 publications

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“…The ability of the G i -protein-coupled receptor to regulate Src kinase activity, and subsequent p42/p44 MAPK kinase activation, has been demonstrated in platelet-derived growth factor receptor activation of cultured airway smooth muscle cells (Conway et al 1999). Our study shows that inhibition of Src tyrosine kinase activity prevents the activation of ROS production in LDL-exposed ECs.…”

Section: Discussionmentioning

confidence: 46%

Endothelial NADPH Oxidase: Mechanism of Activation by Low-Density Lipoprotein

et al. 2003

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Exposure to atherogenic levels of low-density lipoprotein (LDL) causes elevated reactive oxygen species (ROS) production by human endothelial cells (ECs). NADPH oxidase is thought to be the main source of ROS generated by LDL-activated ECs. The mechanism by which this lipoprotein activates endothelial NADPH oxidase is incompletely understood. To gain further insight into the signaling pathway, the authors have examined the effects of inhibitors to various signal transducing enzymes, including the G(i)-protein coupled receptor (pertussis toxin), Src tyrosine kinase (PP1), phospholipase C-gamma (U73122), phosphatidylinositol 3-kinase (LY294002), p42/p44 mitogen-activated protein kinase (MAPK) kinase (PD98059), p38 MAPK (SB203580), protein kinase C (Ro 318220, GF 109203X, Go 6976), and cytosolic phospholipase A(2) (AACOCF3), on the ROS-producing capacity ECs activated by LDL. Exposure of cultured ECs to LDL (0.45 mg protein/mL) stimulated ROS formation, as measured using a 6-carboxy-2',7'-dichlorodihydrofluorescein diacetate assay. This effect was partially inhibited by Ro 318220, GF 109203X, U73122, and SB203580, and blocked or nearly completely inhibited by PP1, pertussis toxin, LY294002, PD98059, and AACOCF3. Only a partial, minor inhibition occurred with the protein kinase C inhibitor, Go 6976. These results are most consistent with LDL activating endothelial NADPH oxidase, predominantly through a signaling pathway that leads to cytosolic phospholipase A(2) activation.

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Section: Discussionmentioning

confidence: 46%

Endothelial NADPH Oxidase: Mechanism of Activation by Low-Density Lipoprotein

et al. 2003

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“…To identify the signaling pathways that mediate g-tocotrienol activity in ASM cells, we examined the p42/p44 mitogen-activated protein kinase (MAPK) and phosphoinositide 3 0 -kinase (PI3K) pathways associated with PDGF-BBeinduced cell proliferation and migration [21,22]. Phosphorylation of p42/p44 MAPK and Akt1 peaked 10e20 min after PDGF-BB stimulation; however 25 mM gtocotrienol did not inhibit activation of p42/p44 MAPK and Akt1 significantly ( Fig.…”

Section: Akt1 and P42/p44 Mapk Phosphorylation Is Not Associated Withmentioning

confidence: 99%

γ-Tocotrienol reduces human airway smooth muscle cell proliferation and migration

Harada

Yamasaki

Chikumi

et al. 2015

Pulmonary Pharmacology & Therapeutics

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“…ASM cells represent a useful model for investigating the mechanisms of co-mitogenic signalling, since pertussis toxin reduces PDGF-stimulated activation of c-Src/p42/p44 MAPK (c-Src is implicated in the regulation of the p42/ p44 MAPK pathway in these cells) by 50 %, thereby suggesting a role for a GPCR-mediated pathway [11]. In the first instance, several new lines of evidence were obtained to support the existence of a functionally active native PDGFβ receptor-S1P 1 receptor complex in ASM cells [12].…”

Section: S1p/pdgf Signalling In Cultured Asm (Airway Smooth Muscle) Cmentioning

confidence: 99%

Receptor tyrosine kinase–GPCR signal complexes

Pyne

Waters

Moughal

et al. 2003

Biochemical Society Transactions

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The formation of complexes between growth factor receptors and members of a family of G-protein-coupled receptors whose natural ligands are S1P (sphingosine 1-phosphate) and LPA (lysophosphatidic acid) represents a new signalling entity. This receptor complex allows for integrated signalling in response to growth factor and/or S1P/LPA and provides a mechanism for more efficient activation (due to integrated close-proximity signalling from both receptor classes) of the p42/p44 MAPK (mitogen-activated protein kinase) pathway. This article provides information on the molecular events at the interface between receptor tyrosine kinases and S1P/LPA receptors. Examples include the PDGF (platelet-derived growth factor)-induced tyrosine phosphorylation of G(i)alpha, released upon S1P(1) receptor activation, which is required for initiation of the p42/p44 MAPK pathway. Critical to this event is the formation of endocytic vesicles containing functionally active PDGFbeta receptor-S1P(1) receptor complexes, which are internalized and relocated with components of the p42/p44 MAPK pathway. We also report examples of cross-talk signal integration between the Trk A (tropomyosin receptor kinase A) receptor and the LPA(1) receptor in terms of the NGF (nerve growth factor)-dependent regulation of the p42/p44 MAPK pathway. NGF induces recruitment of the LPA(1) receptor to the nucleus (delivery might be Trk A-dependent), whereupon the LPA(1) receptor may govern gene expression via novel nuclear signalling processes.

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Platelet-derived-growth-factor stimulation of the p42/p44 mitogen-activated protein kinase pathway in airway smooth muscle: role of pertussis-toxin-sensitive G-proteins, c-Src tyrosine kinases and phosphoinositide 3-kinase

Cited by 86 publications

References 17 publications

Endothelial NADPH Oxidase: Mechanism of Activation by Low-Density Lipoprotein

Endothelial NADPH Oxidase: Mechanism of Activation by Low-Density Lipoprotein

γ-Tocotrienol reduces human airway smooth muscle cell proliferation and migration

Receptor tyrosine kinase–GPCR signal complexes

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