Characterization of hsp27 kinases activated by elevated aortic pressure in heart

Boivin, Benoît; Khairallah, Maya; Cartier, Raymond; Allen, Bruce G.

doi:10.1007/s11010-012-1420-x

Cited by 7 publications

(5 citation statements)

References 77 publications

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“…The protein is phosphorylated on three residues (Ser15, Ser78, and Ser82) by MAPKAP kinase 2/3/5 via the activation of p38MAPK pathway 34 . Other kinases, such as PKB, PKC, PKD, and PKG also independently phosphorylate HSP-27 35 . In fact, in SH-SY5Y human neuroblastoma cells, carbachol-dependent HSP-27 phosphorylation on Ser82 and Ser78 residues are prevented by PKC and p38MAPK inhibition, and phorbol esters-dependent HSP-27(Ser82) phosphorylation is reversed by PKC or PKD inhibitors 36 .…”

Section: Resultsmentioning

confidence: 99%

Phosphoproteomic analysis sheds light on intracellular signaling cascades triggered by Formyl-Peptide Receptor 2

Cattaneo

Russo

Castaldo

et al. 2019

Sci Rep

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Formyl peptide receptors (FPRs) belong to the family of seven transmembrane Gi-protein coupled receptors (GPCR). FPR2 is considered the most promiscuous member of this family since it recognizes a wide variety of ligands. It plays a crucial role in several physio-pathological processes and different studies highlighted the correlation between its expression and the higher propensity to invasion and metastasis of some cancers. FPR2 stimulation by its synthetic agonist WKYMVm triggers multiple phosphorylations of intracellular signaling molecules, such as ERKs, PKC, PKB, p38MAPK, PI3K, PLC, and of non-signaling proteins, such as p47phox and p67phox which are involved in NADPH oxidase-dependent ROS generation. Biological effects of FPR2 stimulation include intracellular Ca2+ mobilization, cellular proliferation and migration, and wound healing. A systematic analysis of the phosphoproteome in FPR2-stimulated cells has not been yet reported. Herein, we describe a large-scale phosphoproteomic study in WKYMVm-stimulated CaLu-6 cells. By using high resolution MS/MS we identified 290 differentially phosphorylated proteins and 53 unique phosphopeptides mapping on 40 proteins. Phosphorylations on five selected phospho-proteins were further validated by western blotting, confirming their dependence on FPR2 stimulation. Interconnection between some of the signalling readout identified was also evaluated. Furthermore, we show that FPR2 stimulation with two anti-inflammatory agonists induces the phosphorylation of selected differentially phosphorylated proteins, suggesting their role in the resolution of inflammation. These data provide a promising resource for further studies on new signaling networks triggered by FPR2 and on novel molecular drug targets for human diseases.

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Section: Resultsmentioning

confidence: 99%

Phosphoproteomic analysis sheds light on intracellular signaling cascades triggered by Formyl-Peptide Receptor 2

Cattaneo

Russo

Castaldo

et al. 2019

Sci Rep

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“…These kinases phosphorylate p38MAPK (p38a), which in turn activates MAPKAPK kinases 2/3/5 (Moens et al 2013). Other kinases including PKB, PKC, PKD and PKG also known to phosphorylate Hsp27 independently (Boivin et al 2012). The two serine residues at positions 78 and 82 are known to be the predominant sites of phosphorylation in Hsp27, and Ser82 is conserved throughout the animal kingdom, whereas Ser78 is replaced by asparagine in number of animals (Landry et al 1992).…”

Section: Discussionmentioning

confidence: 99%

Increased expression of phosphorylated forms of heat‐shock protein‐27 and p38MAPK in macrophage‐rich regions of fibro‐fatty atherosclerotic lesions in the rabbit

Shafi

Codrington²,

Gidden

et al. 2016

Int J Experimental Path

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Summary We aimed to assess the expression and distribution of Hsp27, pHsp27 (Ser82), p38MAPK and p‐p38MAPK in fibro‐fatty atherosclerotic lesions and the myocardium of hypercholesterolaemic rabbits. Male New Zealand white rabbits were fed a high‐cholesterol diet for 18 weeks, maintaining serum cholesterol at approximately 20 mmol/l over this period. Aortic arch and myocardial tissues were analysed by Western blot, immunohistochemistry and double immunofluorescence. Plasma Hsp27 levels were measured by ELISA. There was a significant increase in the expression of monomeric and dimeric forms of Hsp27, together with pHsp27 (Ser82), p38MAPK and p‐p38MAPK in the fibro‐fatty atherosclerotic lesions (P < 0.01; P < 0.05; P < 0.001; and P < 0.001, respectively) and the myocardial tissues (P < 0.001) from the cholesterol‐fed rabbits compared with equivalent tissues from controls when the plasma concentration was low. Immunohistochemical analysis of the fibro‐fatty lesions showed marked increases in Hsp27 and pHsp27 (Ser82) immunoreactivity. Double immunostaining showed intense expression of pHsp27 and p‐p38MAPK in regions that were rich in macrophages, suggesting a close association with these inflammatory cells, whereas, in regions rich in smooth muscle cells, only p‐p38MAPK was found to be strongly expressed. An increased expression of pHsp27 (Ser82) was spatially associated with increased p‐p38MAPK within fibro‐fatty atherosclerotic lesions and was colocalized to regions rich in macrophages. The initial increase in plasma Hsp27 levels may reflect the increase in systemic inflammation and oxidative stress in the early phases of disease. The falling concentrations subsequently may be coincident with the development of the advanced atherosclerotic lesions.

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“…In T. cruzi , TcMVK is located in glycosomes and in addition to its classical function, TcMVK is secreted by EAs, adheres to host cell membrane and positively modulates their uptake by HeLa cells ( Ferreira et al, 2016 ). Treating mammalian cells with recombinant TcMVK triggers ERK, P38 (p38 mitogen activated protein kinase), FAK (focal adhesion kinase) and PAK (p21-activated kinase), which are important regulators of actin cytoskeleton remodeling although their specific role in host cell actin signaling during EA invasion still remains elusive ( Benndorf et al, 1994 ; Procópio et al, 1998 ; Vidal et al, 2002 ; Brunton et al, 2004 ; Boivin et al, 2012 ; Navratil et al, 2014 ; Ferreira et al, 2016 ).…”

Section: Parasite Ingredients: Amastin P21 Tcmvk Ssp-4 and Microvementioning

confidence: 99%

Amastigote Synapse: The Tricks of Trypanosoma cruzi Extracellular Amastigotes

et al. 2018

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To complete its life cycle within the mammalian host, Trypanosoma cruzi, the agent of Chagas’ disease, must enter cells. Trypomastigotes originating from the insect vector (metacyclic) or from infected cells (bloodstream/tissue culture-derived) are the classical infective forms of the parasite and enter mammalian cells in an actin-independent manner. By contrast, amastigotes originating from the premature rupture of infected cells or transformed from swimming trypomastigotes (designated extracellular amastigotes, EAs) require functional intact microfilaments to invade non-phagocytic host cells. Earlier work disclosed the key features of EA-HeLa cell interplay: actin-rich protrusions called ‘cups’ are formed at EA invasion sites on the host cell membrane that are also enriched in actin-binding proteins, integrins and extracellular matrix elements. In the past decades we described the participation of membrane components and secreted factors from EAs as well as the actin-regulating proteins of host cells involved in what we propose to be a phagocytic-like mechanism of parasite uptake. Thus, regarding this new perspective herein we present previously described EA-induced ‘cups’ as parasitic synapse since they can play a role beyond its architecture function. In this review, we focus on recent findings that shed light on the intricate interaction between extracellular amastigotes and non-phagocytic HeLa cells.

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Characterization of hsp27 kinases activated by elevated aortic pressure in heart

Cited by 7 publications

References 77 publications

Phosphoproteomic analysis sheds light on intracellular signaling cascades triggered by Formyl-Peptide Receptor 2

Phosphoproteomic analysis sheds light on intracellular signaling cascades triggered by Formyl-Peptide Receptor 2

Increased expression of phosphorylated forms of heat‐shock protein‐27 and p38MAPK in macrophage‐rich regions of fibro‐fatty atherosclerotic lesions in the rabbit

Amastigote Synapse: The Tricks of Trypanosoma cruzi Extracellular Amastigotes

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