Identification of mannose receptor as receptor for hepatocyte growth factor ß-chain: novel ligand-receptor pathway for enhancing macrophage phagocytosis.
AuthorsOhnishi H, Oka K, Mizuno S, Nakamura T
JournalJ Biol Chem
PubMed ID22354962
'Hepatocyte growth factor (HGF), a heterodimer composed of the a-chain and ß-chain, exerts multifunctional actions for tissue repair and homeostasis via its receptor, MET. HGF is cleaved by proteases secreted from inflammatory cells, and NK4 and ß-chain remnant (HGF-ß) are generated. Here, we provide evidence that HGF-ß binds to a ... More
Anti-human activin receptor-like kinase 1 (ALK1) antibody attenuates bone morphogenetic protein 9 (BMP9)-induced ALK1 signaling and interferes with endothelial cell sprouting.
Authorsvan Meeteren LA, Thorikay M, Bergqvist S, Pardali E, Stampino CG, Hu-Lowe D, Goumans MJ, ten Dijke P
JournalJ Biol Chem
PubMed ID22493445
'Genetic and molecular studies suggest that activin receptor-like kinase 1 (ALK1), a transforming growth factor ß (TGF-ß) type I receptor, and endoglin, a TGF-ß co-receptor, play an essential role in vascular development and pathological angiogenesis. Several agents that interfere with ALK1 and endoglin function are currently in clinical trials for ... More
Tight complex formation between Cosmc chaperone and its specific client non-native T-synthase leads to enzyme activity and client-driven dissociation.
AuthorsAryal RP, Ju T, Cummings RD
JournalJ Biol Chem
PubMed ID22416136
'The interaction of the endoplasmic reticulum molecular chaperone Cosmc with its specific client T-synthase (Core 1 ß1-3-galactosyltransferase) is required for folding of the enzyme and eventual movement of the T-synthase to the Golgi, but the mechanism of interaction is unclear. Here we show that the lumenal domain of recombinant Cosmc ... More
Resolving nitrogen-15 and proton chemical shifts for mobile segments of elastin with two-dimensional NMR spectroscopy.
In this study, one- and two-dimensional NMR experiments are applied to uniformly (15)N-enriched synthetic elastin, a recombinant human tropoelastin that has been cross-linked to form an elastic hydrogel. Hydrated elastin is characterized by large segments that undergo "liquid-like" motions that limit the efficiency of cross-polarization. The refocused insensitive nuclei enhanced ... More
The tumor necrosis factor receptor stalk regions define responsiveness to soluble versus membrane-bound ligand.
AuthorsRichter C, Messerschmidt S, Holeiter G, Tepperink J, Osswald S, Zappe A, Branschädel M, Boschert V, Mann DA, Scheurich P, Krippner-Heidenreich A,
JournalMol Cell Biol
PubMed ID22547679
The family of tumor necrosis factor receptors (TNFRs) and their ligands form a regulatory signaling network that controls immune responses. Various members of this receptor family respond differently to the soluble and membrane-bound forms of their respective ligands. However, the determining factors and underlying molecular mechanisms of this diversity are ... More
Dimerization of plant defensin NaD1 enhances its antifungal activity.
AuthorsLay FT, Mills GD, Poon IK, Cowieson NP, Kirby N, Baxter AA, van der Weerden NL, Dogovski C, Perugini MA, Anderson MA, Kvansakul M, Hulett MD
JournalJ Biol Chem
PubMed ID22511788
The plant defensin, NaD1, from the flowers of Nicotiana alata, is a member of a family of cationic peptides that displays growth inhibitory activity against several filamentous fungi, including Fusarium oxysporum. The antifungal activity of NaD1 has been attributed to its ability to permeabilize membranes; however, the molecular basis of ... More
Rational design and characterization of platelet factor 4 antagonists for the study of heparin-induced thrombocytopenia.
Patients with heparin-induced thrombocytopenia (HIT) remain at risk for recurrent thromboembolic complications despite improvements in management. HIT is caused by antibodies that preferentially recognize ultralarge complexes (ULCs) of heparin and platelet factor 4 (PF4) tetramers. We demonstrated previously that a variant PF4(K50E) forms dimers but does not tetramerize or form ... More
A conserved motif in the C-terminal tail of DNA polymerase a tethers primase to the eukaryotic replisome.
AuthorsKilkenny ML, De Piccoli G, Perera RL, Labib K, Pellegrini L
JournalJ Biol Chem
PubMed ID22593576
The DNA polymerase a-primase complex forms an essential part of the eukaryotic replisome. The catalytic subunits of primase and pol a synthesize composite RNA-DNA primers that initiate the leading and lagging DNA strands at replication forks. The physical basis and physiological significance of tethering primase to the eukaryotic replisome via ... More