Stressed platelets ASK1 for a MAPK

Flaumenhaft, Robert

doi:10.1182/blood-2017-01-760546

Cited by 10 publications

(7 citation statements)

References 10 publications

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“…These results show that inhibition of PP2A regulates the phosphorylation and activation of several pathways such as cytoskeletal adaptor proteins (VASP), proteins related to MAPK signalling (MEK, Erk, p38) and PI3K/Akt signalling components. While phosphorylation of VASP, a PKA/PKG substrate, is closely associated with the inhibition of platelet activation [80,81], phosphorylation and activation of MEK, Erk and p38 in platelets is especially important for initiation of platelet activation [51,76,[82][83][84] and Akt phosphorylation/activation for amplifying of platelet activation responses [85]. The observed increased phosphorylation of p38 with 200 nM of OA is of considerable interest, since it is well known that there is an extensive cross-talk between p38, other MAP kinases and PP2A [74].…”

Section: Ser-phosphorylated Arpp19 Is Both a Substrate For And Inhibimentioning

confidence: 99%

The Cell Cycle Checkpoint System MAST(L)-ENSA/ARPP19-PP2A is Targeted by cAMP/PKA and cGMP/PKG in Anucleate Human Platelets

Kumm

Pagel

Gambaryan

et al. 2020

Cells

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The cell cycle is controlled by microtubule-associated serine/threonine kinase-like (MASTL), which phosphorylates the cAMP-regulated phosphoproteins 19 (ARPP19) at S62 and 19e/α-endosulfine (ENSA) at S67and converts them into protein phosphatase 2A (PP2A) inhibitors. Based on initial proteomic data, we hypothesized that the MASTL-ENSA/ARPP19-PP2A pathway, unknown until now in platelets, is regulated and functional in these anucleate cells. We detected ENSA, ARPP19 and various PP2A subunits (including seven different PP2A B-subunits) in proteomic studies of human platelets. ENSA-S109/ARPP19–S104 were efficiently phosphorylated in platelets treated with cAMP- (iloprost) and cGMP-elevating (NO donors/riociguat) agents. ENSA-S67/ARPP19-S62 phosphorylations increased following PP2A inhibition by okadaic acid (OA) in intact and lysed platelets indicating the presence of MASTL or a related protein kinase in human platelets. These data were validated with recombinant ENSA/ARPP19 and phospho-mutants using recombinant MASTL, protein kinase A and G. Both ARPP19 phosphorylation sites S62/S104 were dephosphorylated by platelet PP2A, but only S62-phosphorylated ARPP19 acted as PP2A inhibitor. Low-dose OA treatment of platelets caused PP2A inhibition, diminished thrombin-stimulated platelet aggregation and increased phosphorylation of distinct sites of VASP, Akt, p38 and ERK1/2 MAP kinases. In summary, our data establish the entire MASTL(like)–ENSA/ARPP19–PP2A pathway in human platelets and important interactions with the PKA, MAPK and PI3K/Akt systems.

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Section: Ser-phosphorylated Arpp19 Is Both a Substrate For And Inhibimentioning

confidence: 99%

The Cell Cycle Checkpoint System MAST(L)-ENSA/ARPP19-PP2A is Targeted by cAMP/PKA and cGMP/PKG in Anucleate Human Platelets

Kumm

Pagel

Gambaryan

et al. 2020

Cells

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“…Furthermore, PGG from R. verniciflua reduced calcium mobilization and expression of P-selectin in human platelets previously activated by ADP ( Jeon et al, 2006 ). In rabbit platelets, bPGG inhibited thrombin-induced phosphorylation and subsequent activation of phospholipase Cβ (PLCβ), leading to the secretion of dense granules ( Lee et al, 2014 ; Flaumenhaft, 2017 ). It has also been shown that aPGG bound to the insulin receptor on the surface of human platelets and caused a reduction in their activity similar to insulin ( Perveen et al, 2011 ).…”

Section: Tannins and Plateletsmentioning

confidence: 99%

“…• A-type procyanidins: dimer procyanidins with C4-C8 interflavan bond and an additional C2-C7 ether bond secretion of dense granules (Lee et al, 2014;Flaumenhaft, 2017). It has also been shown that aPGG bound to the insulin receptor on the surface of human platelets and caused a reduction in their activity similar to insulin (Perveen et al, 2011).…”

Section: Structurementioning

confidence: 99%

Tannins as Hemostasis Modulators

Marcińczyk

Gromotowicz-Popławska

Chabielska

2022

Front. Pharmacol.

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The hemostasis system is often affected by complications associated with cardiovascular diseases, which results in thromboembolic events. Compounds of plant origin and plant extracts are considered as a promising source of substances that could modulate the functioning of the hemostasis system and thus reduce the risk of thromboembolism. Among them, tannins, which are plant-origin compounds with potential effects in hemostasis, deserve a special mention. This paper describes the hemostasis-modifying ability of three groups of tannins, namely ellagitannins, gallotannins, and procyanidins. The review highlights the desirable as well as undesirable influence of tannins on specific components of hemostasis, namely platelets, coagulation system, fibrinolysis system, and endothelium, and the multidirectional effect of these compounds on the thrombotic process. Studies performed under normal and pathological conditions such as diabetes or hypercoagulation are described, and the pathophysiology-dependent action of tannins is also highlighted. Most of the studies presented in the paper were performed in vitro, and due to the low bioavailability of tannins more studies should be conducted in the future to understand their actual activity in vivo.

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“…Apoptosis signal-regulating kinase 1 (ASK1), a member of the mitogen-activated protein kinase kinase kinase (MAP3K) family, is an important stress responsive protein kinase which plays a crucial role in the initiation of numerous diseases, including neurodegenerative, cardiovascular, inflammatory, autoimmunity, and metabolic disorders ( 12 , 13 ). The MAPK member, p38, is a serine/threonine protein kinase, which responds to several cellular processes and external stress signaling, such as cell differentiation, cell proliferation, inflammation regulation and cell death ( 14 , 15 ). ASK1 is the most well-studied family member and is an upstream kinase of the JNK and p38 pathways ( 16 , 17 ).…”

Section: Introductionmentioning

confidence: 99%

ASK1/p38‑mediated NLRP3 inflammasome signaling pathway contributes to aberrant retinal angiogenesis in diabetic retinopathy

et al. 2020

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Diabetic retinopathy (DR) is the leading cause of blindness among the working-age population in several countries. Despite the available treatments, some patients are diagnosed at the late stages of the disease when treatment is more difficult. Hence, it is crucial that novel targets are identified in order to improve the clinical therapy of DR. In the present study, an animal model of DR and a cell model using primary human retinal microvascular endothelial cells exposed to high glucose were constructed to examine the association between apoptosis signal-regulating kinase 1 (ASK1)/p38 and NLR family pyrin domain containing 3 (NLRP3) in DR. The results revealed that DR induced inflammatory response and micro-vascular cell proliferation. NLRP3 contributed to DR-mediated inflammatory development and progression, which promoted the expression of inflammatory-related cytokines. In addition, NLRP3 promoted the tube formation of retinal microvascular endothelial cells and angiogenesis. Moreover, further research indicated that the NLRP3-mediated aberrant retinal angiogenesis in DR was regulated by ASK1 and p38. It was thus suggested that ASK1/p38 may be novel target for the treatment of DR.

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Stressed platelets ASK1 for a MAPK

Cited by 10 publications

References 10 publications

The Cell Cycle Checkpoint System MAST(L)-ENSA/ARPP19-PP2A is Targeted by cAMP/PKA and cGMP/PKG in Anucleate Human Platelets

The Cell Cycle Checkpoint System MAST(L)-ENSA/ARPP19-PP2A is Targeted by cAMP/PKA and cGMP/PKG in Anucleate Human Platelets

Tannins as Hemostasis Modulators

ASK1/p38‑mediated NLRP3 inflammasome signaling pathway contributes to aberrant retinal angiogenesis in diabetic retinopathy

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