Search results for " Post-Translational"
showing 10 items of 148 documents
Modeling Human Endometrial Decidualization from the Interaction between Proteome and Secretome
2011
Context: Decidualization of the human endometrium, which involves morphological and biochemical modifications of the endometrial stromal cells (ESCs), is a prerequisite for adequate trophoblast invasion and placenta formation. Objective: This study aims to investigate the proteome and secretome of in vitro decidualized ESCs. These data were combined with published genomic information and integrated to model the human decidualization interactome. Design: Prospective experimental case–control study. Setting: A private research foundation. Patients: Sixteen healthy volunteer ovum donors. Intervention: Endometrial samples were obtained, and ESCs were isolated and decidualized in vitro. Main Ou…
Natural Proteolytic Processing of Hemofiltrate Cc Chemokine 1 Generates a Potent Cc Chemokine Receptor (Ccr)1 and Ccr5 Agonist with Anti-HIV Properti…
2000
Hemofiltrate CC chemokine (HCC)-1 is a recently described human chemokine that is constitutively expressed in numerous tissues and is present at high concentrations in normal plasma. Using a cell line expressing CC chemokine receptor (CCR)5 as a bioassay, we isolated from human hemofiltrate an HCC-1 variant lacking the first eight amino acids. HCC-1[9–74] was a potent agonist of CCR1, CCR3, and CCR5 and promoted calcium flux and chemotaxis of T lymphoblasts, monocytes, and eosinophils. It also blocked entry of HIV-1 strains using CCR5 as coreceptor. Limited tryptic digestion of HCC-1 generated the active variant. Conditioned media from several tumor cell lines activated HCC-1 with a high ef…
Elevated Protein Content and Prolyl 4-Hydroxylase Activity in Severely Degenerated Human Annulus Fibrosus
2000
Alterations involved with the intervertebral disc degeneration are partly well described, however, it is not so well known how collagen network is affected by the disease. We analyzed the rate of collagen biosynthesis (estimated by the enzymic activities of prolyl 4-hydroxylase and galactosylhydroxylysyl glucosyltransferase) and the level of hydroxylysylpyridinoline and lysylpyridinoline crosslinks both in normal (n=7) and degenerated (n=7) human annulus fibrosus. The activity of prolyl 4-hydroxylase was significantly increased in degenerated tissue. However, no significant changes in the collagen content or in the amount of hydroxylysylpyridinoline and lysylpyridinoline collagen crosslinks…
Assessment of determinants affecting the dual topology of hepadnaviral large envelope proteins
2004
For functional diversity, the large (L) envelope protein of hepatitis B virus (HBV) acquires a dual transmembrane topology via co-translational membrane integration of the S region and partial post-translational translocation of the preS subdomain. Because each process requires the second transmembrane segment (TM2), we explored the action of this determinant by using protease protection analysis of mutant L proteins. We demonstrated that neither the disruption of a leucine zipper-like motif by multiple alanine substitutions nor the flanking charges of TM2 affected the topological reorientation of L. The dispensability of both putative subunit interaction modules argues against a link betwe…
Phosphorylation of serine residues is fundamental for the calcium-binding ability of Orchestin, a soluble matrix protein from crustacean calcium stor…
2003
International audience; Orchestia cavimana is a terrestrial crustacean, which cyclically stores calcium in diverticula of the midgut, in the form of calcified amorphous concretions. These concretions are associated with a proteinaceous matrix, the main constituent of the soluble matrix is Orchestin, an acidic calcium-binding protein [Testenière et al., Biochem. J. 361 (2002) 327-335]. In the present paper, we clearly demonstrate that Orchestin is phosphorylated on serine and tyrosine residues, but that calcium binding only occurs via the phosphoserine residues. To our knowledge, this is the first example of an invertebrate mineralization for which a post-translational modification is clearl…
Phosphorylation of cytochromes P450: First discovery of a posttranslational modification of a drug-metabolizing enzyme
2005
Cytochromes P450 (CYP) are important components of xenobiotic-metabolizing monooxygenases (CYP-dependent monooxygenases). Their regulation by induction, most commonly by transcriptional activation, mediated by xenobiotics, normally substrates of the corresponding CYP, is well known and has been widely studied. Our team has discovered an additional important regulation of xenobiotic-metabolizing CYPs pertaining to posttranslational modification by phosphorylation. Individual CYPs are phosphorylated by different protein kinases, leading to CYP isoenzyme-selective changes in the metabolism of individual substrates and consequent drastic changes in the control of genotoxic metabolites. Best stu…
Cleavage of endometrial α-integrins into their functional forms is mediated by proprotein convertase 5/6.
2012
Background Proprotein convertases (PCs) post-translationally activate a large number of protein precursors through limited cleavage. PC5/6 (PC6) in the human endometrium is tightly regulated during receptivity for embryo implantation. Integrins are transmembrane glycoproteins, some of which play an important role in the adhesive interactions between the trophoblast (blastocyst) and uterine epithelium at implantation. Integrins require PC cleavage for post-translational modification. We hypothesize that pro-integrin-αs in the endometrial epithelium are post-translationally cleaved by PC6 into functional subunits for the binding of blastocyst and adhesion of extracellular matrix proteins. Met…
The histone deacetylase sirtuin 2 is a new player in the regulation of platelet function
2015
SummaryBackground Histone deacetylases (HDACs) play a key role in signaling in many cell types. However, little is known about the participation of HDACs, particularly sirtuins (SIRTs), in platelet reactivity. Objective To investigate the role of HDACs in platelets, we examined the effects of SIRT inhibition on platelet function and protein acetylation in human platelets. Methods We used washed platelets obtained from healthy subjects. Cambinol (SIRT1 and SIRT2 inhibitor), AGK2 (specific SIRT2 inhibitor) and EX527 (specific SIRT1 inhibitor) were used as SIRT inhibitors. Platelets were stimulated with collagen, thrombin, or U46619, and platelet responses were determined according to optical …
Deciphering of ADP-induced, phosphotyrosine-dependent signaling networks in human platelets by Src-homology 2 region (SH2)-profiling.
2012
Tyrosine phosphorylation plays a central role in signal transduction controlling many important biological processes. In platelets, the activity of several signaling proteins is controlled by tyrosine phosphorylation ensuring proper platelet activation and aggregation essential for regulation of the delicate balance between bleeding and hemostasis. Here, we applied Src-homology 2 region (SH2)-profiling for deciphering of the phosphotyrosine state of human platelets activated by adenosine diphosphate (ADP). Applying a panel of 31 SH2-domains, rapid and complex regulation of the phosphotyrosine state of platelets was observed after ADP stimulation. Specific inhibition of platelet P2Y receptor…
Molecular Proteomics and Signalling of Human Platelets in Health and Disease
2021
Platelets are small anucleate blood cells that play vital roles in haemostasis and thrombosis, besides other physiological and pathophysiological processes. These roles are tightly regulated by a complex network of signalling pathways. Mass spectrometry-based proteomic techniques are contributing not only to the identification and quantification of new platelet proteins, but also reveal post-translational modifications of these molecules, such as acetylation, glycosylation and phosphorylation. Moreover, target proteomic analysis of platelets can provide molecular biomarkers for genetic aberrations with established or non-established links to platelet dysfunctions. In this report, we review …