43 research outputs found
The biology of a prostate cancer metastasis suppressor protein: Raf kinase inhibitor protein
Raf kinase inhibitor protein (RKIP) was originally identified as a protein that bound membrane phospholipids and was named phosphatidylethanolamine binding protein-2 (PEBP-2). RKIP was than identified as a protein that bound Raf and blocked its ability to phosphorylate MEK, thus earning its new name of RKIP. Subsequent to identification of its role in the Raf:MEK pathway, RKIP has been demonstrated to regulate several other signaling pathways including G-protein signaling and NF-ΚB signaling. Its involvement in several signaling pathways has engendered RKIP to contribute to several physiological processes including membrane biosynthesis, spermatogenesis, neural development, and apoptosis. RKIP is expressed in many tissues including brain, lung, and liver and thus, dysregulation of RKIP expression or function has potential to contribute to pathophysiology in these tissues. Loss of RKIP expression in prostate cancer cells confers a metastatic phenotype on them. Additionally, restoration of RKIP expression in a metastatic prostate cancer cell line does not effect primary tumor growth, but it does inhibit prostate cancer metastasis. These parameters identify RKIP as a metastasis suppressor gene. In this review, the biology and pathophysiology of RKIP is described. © 2004 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34907/1/20169_ftp.pd
Ligand Binding Study of Human PEBP1/RKIP: Interaction with Nucleotides and Raf-1 Peptides Evidenced by NMR and Mass Spectrometry
Background
Human Phosphatidylethanolamine binding protein 1 (hPEBP1) also known as Raf kinase inhibitory protein (RKIP), affects various cellular processes, and is implicated in metastasis formation and Alzheimer's disease. Human PEBP1 has also been shown to inhibit the Raf/MEK/ERK pathway. Numerous reports concern various mammalian PEBP1 binding ligands. However, since PEBP1 proteins from many different species were investigated, drawing general conclusions regarding human PEBP1 binding properties is rather difficult. Moreover, the binding site of Raf-1 on hPEBP1 is still unknown.
Methods/Findings
In the present study, we investigated human PEBP1 by NMR to determine the binding site of four different ligands: GTP, FMN, and one Raf-1 peptide in tri-phosphorylated and non-phosphorylated forms. The study was carried out by NMR in near physiological conditions, allowing for the identification of the binding site and the determination of the affinity constants KD for different ligands. Native mass spectrometry was used as an alternative method for measuring KD values.
Conclusions/Significance
Our study demonstrates and/or confirms the binding of hPEBP1 to the four studied ligands. All of them bind to the same region centered on the conserved ligand-binding pocket of hPEBP1. Although the affinities for GTP and FMN decrease as pH, salt concentration and temperature increase from pH 6.5/NaCl 0 mM/20°C to pH 7.5/NaCl 100 mM/30°C, both ligands clearly do bind under conditions similar to what is found in cells regarding pH, salt concentration and temperature. In addition, our work confirms that residues in the vicinity of the pocket rather than those within the pocket seem to be required for interaction with Raf-1.METASU
Pärlor ur jorden : En jämförande studie av platserna Uppåkra, Skåne och Sorte Muld, Bornholm utifrån det pärlmaterial som finns för att utröna regionala likheter eller skillnader.
En jämförande studie av glaspärlor från Uppåkra och Sorte Muld för att hitta regionala likheter eller skillnader. Studien visar en skandinavisk gemenskap, en möjlig lokal tillverkning och handel. Diskuterar fortsatt forskning kring datering av glaspärlor
Le scorbut à l'hopital Cochin pendant le siége de Paris : mémoire lu à la Société médicale des Hôpitaux ; dans la séance du 28 avril 1871
par J. Bucquo
Le Veritable Esprit De La Belle Gloire Ou Le Soin De Se Faire Une Bonne Reputation : ... Mit hin und wieder eingemischten Versen verfasset
Par Monsieuur Le Comte De Buquoit. Aus dem Französischen ins Hochteutsche übersetzt und in beyden Sprachen ans Licht gestellet von M. J. F. S.Autopsie nach Ex. der ULB Sachsen-AnhaltVorlageform des Erscheinungsvermerks: Anno 1735. - Kolophon: Cet ouvrage ... se trouve gratis â Herrenhausen, chéz l'Agent de L'Auteur & particulierement en faveur des Gens dela Cour.Text in franz. und dt
Événement des plus rares ou l'Histoire du Sr. abbé Cte de Buquoy singulièrement son évasion du Fort-l'Évêque et de la Bastille, l'allemand à côté, revüe et augmentée, deuxiéme édition avec plusieurs de ses ouvrages vers et prose & particululiéremnt [sic] la Game des femmes.
De Diev De La Vraie Et Favsse Religion En General Stances Irregvlieres : [Hernhausen d. 18 mai. 1732]
[L. Cte. de Buquoit]Autopsie nach Ex. der ULB Sachsen-AnhaltVorlageform des Erscheinungsvermerks: Hannover, Chez Nicolas Foerster Et Fils. 173