Activation of Phospholipase Cγ2 by Tyrosine Phosphorylation

Özdener, Fatih; Dangelmaier, Carol; Ashby, Barrie; Kunapuli, Satya P.; Daniel, James L.

doi:10.1124/mol.62.3.672

Cited by 58 publications

(45 citation statements)

References 36 publications

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“…In contrast, thrombin and 2-MeS-ADP, as expected, had no or only weak effects on LAT tyrosine phosphorylation. However, and in consequence, we found that Pam3CSK4 promoted marked PLC2 phosphorylation at Tyr759 residues, the latter which has been reported to be associated with human platelet activation in response to collagen [36].…”

Section: Platelet Activation Induced By Thrombin Via Pars or Collagensupporting

confidence: 55%

The Toll-like receptor 2/1 (TLR2/1) complex initiates human platelet activation via the src/Syk/LAT/PLCγ2 signalling cascade

Fälker

Klarström-Engström

Bengtsson

et al. 2014

Cellular Signalling

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Section: Platelet Activation Induced By Thrombin Via Pars or Collagensupporting

confidence: 55%

The Toll-like receptor 2/1 (TLR2/1) complex initiates human platelet activation via the src/Syk/LAT/PLCγ2 signalling cascade

Fälker

Klarström-Engström

Bengtsson

et al. 2014

Cellular Signalling

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“…Phospholipase C gamma-2 (PLCγ-2) has been implicated in collagen-induced signal transduction in platelets and antigen-dependent signaling in B-lymphocytes (Ozdener et al, 2002) Our results show an increase in the phosphorylation of PLCγ-2 on Tyr 759 site, following treatment with PPD and stimulation with low doses of collagen, suggesting the involvement of PPD in platelet activation.…”

Section: Discussionmentioning

confidence: 58%

Paraphenylene diamine exacerbates platelet aggregation and thrombus formation in response to a low dose of collagen

et al. 2016

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-Paraphenylene daimine (PPD) is an aromatic amine that is widely used in several industrial products; however, its toxicity has been reported in several cases of cardiac arrests. As platelets play a key role in cardiovascular diseases, we aimed to determine the impact of PPD in vitro and in vivo on platelet function. Our findings demonstrated that platelet activation and aggregation were strongly enhanced by PPD. Treatment with PPD primed human platelets that became more reactive in response to low doses of collagen. Furthermore, PPD exacerbated thrombus formation in rats in comparison with those untreated. Our results suggest that PPD is an important platelet primer predisposing platelets to promote thrombus formation in response to vascular injury. This should prompt the authorities to consider controlling the marketing of this product.

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“…7B). PLC␥ 1 is universally expressed in most tissues (46), whereas PLC␥ 2 is an inducible isoform (35). Strong expression of PLC␥ 1 (140 kDa) appeared in RA-ECs and a much weaker signal was detected in RASMCs (Fig.…”

Section: Effects Of Plc Pathway Inhibitors On Vascular Activity In Ramentioning

confidence: 93%

Role of phospholipase C and diacylglyceride lipase pathway in arachidonic acid release and acetylcholine-induced vascular relaxation in rabbit aorta

Tang¹,

Edwards²,

Holmes³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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(ECs). In rabbit aorta, AA is metabolized through the 15-lipoxygenase pathway to form vasodilatory eicosanoids 15-hydroxy-11,12-epoxyeicosatrienoic acid (HEETA) and 11,12,15-trihydroxyeicosatrienoic acid (THETA). AA is released from phosphatidylcholine (PC) and phosphatidylethanolamine (PE) by phospholipase A 2 (PLA2), or from phosphatidylinositol (PI) by phospholipase C (PLC) pathway. The diacylglycerol (DAG) lipase can convert DAG into 2-arachidonoylglycerol from which free AA can be released by monoacylglycerol (MAG) lipase or fatty acid amidohydrolase (FAAH). We used specific inhibitors to determine the involvement of the PLC pathway in ACh-induced AA release. In rabbit aortic rings precontracted by phenylephrine, ACh induced relaxation in the presence of indomethacin and N -nitro-L-arginine (L-NNA). These relaxations were blocked by the PLC inhibitor U-73122, DAG lipase inhibitor RHC-80267, and MAG lipase/FAAH inhibitor URB-532. Cultured rabbit aortic ECs were labeled with [ 14 C]AA and stimulated with methacholine (10 Ϫ5 M). Free [ 14 C]AA was released by methacholine. Methacholine decreased the [ 14 C]AA content of PI, DAG, and MAG fractions but not PC or PE fractions. Methacholine-induced release of [ 14 C]AA was blocked by U-73122, RHC-80267, and URB-532 but not by U-73343, an inactive analog of U-73122. The data suggested that ACh activates PLC, DAG lipase, and MAG lipase pathway to release AA from membrane lipids. This pathway is important in regulating vasodilatory eicosanoid synthesis and vascular relaxation in rabbit aorta. endothelium-dependent hyperpolarizing factor; phospholipid; monoacylglycerol lipase; trihydroxyeicosatrienoic acid; hydroxyepoxyeicosatrienoic acid VASCULAR ENDOTHELIAL CELLS (ECs) regulate vascular tone by synthesis and release of many bioactive compounds. Ligands such as hormones, ACh, bradykinin, and cytokines stimulate release of arachidonic acid (AA) from cellular membranes (6,15,26,43,55), and AA induces endothelium-dependent vasodilation in isolated rabbit aorta preconstricted with phenylephrine, which is not blocked by nitric oxide (NO) synthase (NOS) and cyclooxygenase (COX) inhibitors (19,39,50). The phospholipase inhibitors mepacrine and dimethyl-eicosadienoic acid (DEDA) decrease relaxation to ACh but not AA, suggesting AA or a metabolite may be involved in the relaxations (11). AA is metabolized by COX, lipoxygenase (LO), and cytochrome P-450 pathways into bioactive eicosanoids (10,30,40,48). Using specific inhibitors in rabbit aorta, Singer and Peach (51) first concluded that a LO metabolite mediates the NO-and PG-resistant relaxation to ACh (51). The LO inhibitors cinnamyl-3,4-dihydroxy-␣-cyanocinnamate, nordihydroguaiaretic acid, and ebselen block ACh and AA-induced vasodilation in rabbit aorta (11,39,42). Previous studies in our lab identified the 15-LO metabolites of AA in rabbit aorta. AA is oxidized by 15-LO to 15-hydroperoxyeicosatetraenoic acid (15-HPETE), which is converted to hydroxyepoxyeicosatrienoic acid (HEETA) and trihydroxyeicosatrienoic acid (THET...

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Activation of Phospholipase Cγ2 by Tyrosine Phosphorylation

Cited by 58 publications

References 36 publications

The Toll-like receptor 2/1 (TLR2/1) complex initiates human platelet activation via the src/Syk/LAT/PLCγ2 signalling cascade

The Toll-like receptor 2/1 (TLR2/1) complex initiates human platelet activation via the src/Syk/LAT/PLCγ2 signalling cascade

Paraphenylene diamine exacerbates platelet aggregation and thrombus formation in response to a low dose of collagen

Role of phospholipase C and diacylglyceride lipase pathway in arachidonic acid release and acetylcholine-induced vascular relaxation in rabbit aorta

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