Browsing by Subject "protein"

Now showing 1 - 4 of 4

Open Access
Activating mutations of STAT5B and STAT3 in lymphomas derived from γδ-T or NK cells
(Nature Publishing Group, 2015) Küçük, C.; Jiang, B.; Hu X.; Zhang W.; Chan J.K.C.; Xiao W.; Lack, N.; Alkan, C.; Williams J.C.; Avery, K.N.; Kavak P.; Scuto, A.; Sen, E.; Gaulard P.; Staudt L.; Iqbal J.; Zhang W.; Cornish, A.; Gong Q.; Yang Q.; Sun H.; D'Amore F.; Leppä, S.; Liu W.; Fu, K.; De Leval L.; McKeithan, T.; Chan W.C.
Lymphomas arising from NK or γδ-T cells are very aggressive diseases and little is known regarding their pathogenesis. Here we report frequent activating mutations of STAT3 and STAT5B in NK/T-cell lymphomas (n=51), γδ-T-cell lymphomas (n=43) and their cell lines (n=9) through next generation and/or Sanger sequencing. STAT5B N642H is particularly frequent in all forms of γδ-T-cell lymphomas. STAT3 and STAT5B mutations are associated with increased phosphorylated protein and a growth advantage to transduced cell lines or normal NK cells. Growth-promoting activity of the mutants can be partially inhibited by a JAK1/2 inhibitor. Molecular modelling and surface plasmon resonance measurements of the N642H mutant indicate a marked increase in binding affinity of the phosphotyrosine-Y699 with the mutant histidine. This is associated with the prolonged persistence of the mutant phosphoSTAT5B and marked increase of binding to target sites. Our findings suggest that JAK-STAT pathway inhibition may represent a therapeutic strategy. © 2015 Macmillan Publishers Limited. All rights reserved.
Open Access
Generation of phospholipid vesicle-nanotube networks and transport of molecules therein
(2011) Jesorka, A.; Stepanyants, N.; Zhang H.; Ortmen, B.; Hakonen, B.; Orwar O.
We describe micromanipulation and microinjection procedures for the fabrication of soft-matter networks consisting of lipid bilayer nanotubes and surface-immobilized vesicles. These biomimetic membrane systems feature unique structural flexibility and expandability and, unlike solid-state microfluidic and nanofluidic devices prepared by top-down fabrication, they allow network designs with dynamic control over individual containers and interconnecting conduits. The fabrication is founded on self-assembly of phospholipid molecules, followed by micromanipulation operations, such as membrane electroporation and microinjection, to effect shape transformations of the membrane and create a series of interconnected compartments. Size and geometry of the network can be chosen according to its desired function. Membrane composition is controlled mainly during the self-assembly step, whereas the interior contents of individual containers is defined through a sequence of microneedle injections. Networks cannot be fabricated with other currently available methods of giant unilamellar vesicle preparation (large unilamellar vesicle fusion or electroformation). Described in detail are also three transport modes, which are suitable for moving water-soluble or membrane-bound small molecules, polymers, DNA, proteins and nanoparticles within the networks. The fabrication protocol requires ∼90 min, provided all necessary preparations are made in advance. The transport studies require an additional 60-120 min, depending on the transport regime. © 2011 Nature America, Inc. All rights reserved.
Open Access
GOPred: GO molecular function prediction by combined classifiers
(2010) Saraç Ö.S.; Atalay V.; Cetin-Atalay, R.
Functional protein annotation is an important matter for in vivo and in silico biology. Several computational methods have been proposed that make use of a wide range of features such as motifs, domains, homology, structure and physicochemical properties. There is no single method that performs best in all functional classification problems because information obtained using any of these features depends on the function to be assigned to the protein. In this study, we portray a novel approach that combines different methods to better represent protein function. First, we formulated the function annotation problem as a classification problem defined on 300 different Gene Ontology (GO) terms from molecular function aspect. We presented a method to form positive and negative training examples while taking into account the directed acyclic graph (DAG) structure and evidence codes of GO. We applied three different methods and their combinations. Results show that combining different methods improves prediction accuracy in most cases. The proposed method, GOPred, is available as an online computational annotation tool (http://kinaz.fen.bilkent.edu.tr/gopred). © 2010 Saraç et al.
Open Access
A role for LYNX2 in anxiety-related behavior
(2009) Tekinay, A.B.; Nong, Y.; Miwa J.M.; Lieberam I.; Ibanez-Tallon I.; Greengard P.; Heintz, N.
Anxiety disorders are the most prevalent mental disorders in developed societies. Although roles for the prefrontal cortex, amygdala, hippocampus and mediodorsal thalamus in anxiety disorders are well documented, molecular mechanisms contributing to the functions of these structures are poorly understood. Here we report that deletion of Lynx2, a mammalian prototoxin gene that is expressed at high levels in anxiety associated brain areas, results in elevated anxiety-like behaviors. We show that LYNX2 can bind to and modulate neuronal nicotinic receptors, and that loss of Lynx2 alters the actions of nicotine on glutamatergic signaling in the prefrontal cortex. Our data identify Lynx2 as an important component of the molecular mechanisms that control anxiety, and suggest that altered glutamatergic signaling in the prefrontal cortex of Lynx2 mutant mice contributes to increased anxiety-related behaviors.