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https://www.readbyqxmd.com/read/28220894/inhibition-of-n1-src-kinase-by-a-specific-sh3-peptide-ligand-reveals-a-role-for-n1-src-in-neurite-elongation-by-l1-cam
#1
Sarah Keenan, Sarah J Wetherill, Christopher I Ugbode, Sangeeta Chawla, William J Brackenbury, Gareth J O Evans
In the mammalian brain the ubiquitous tyrosine kinase, C-Src, undergoes splicing to insert short sequences in the SH3 domain to yield N1- and N2-Src. We and others have previously shown that the N-Srcs have altered substrate specificity and kinase activity compared to C-Src. However, the exact functions of the N-Srcs are unknown and it is likely that N-Src signalling events have been misattributed to C-Src because they cannot be distinguished by conventional Src inhibitors that target the kinase domain. By screening a peptide phage display library, we discovered a novel ligand (PDN1) that targets the unique SH3 domain of N1-Src and inhibits N1-Src in cells...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28219718/a-novel-regulatory-role-of-rgs4-in-stat5b-activation-neurite-outgrowth-and-neuronal-differentiation
#2
Paschalina Pallaki, Eirini-Maria Georganta, Ioannis Serafimidis, Maria-Pagona Papakonstantinou, Vassilis Papanikolaou, Sofia Koutloglou, Elsa Papadimitriou, Adamantia Agalou, Aggeliki Tserga, Alexandra Simeonof, Dimitra Thomaidou, Maria Gaitanou, Zafiroula Georgoussi
The Regulator of G protein Signalling 4 (RGS4) is a multitask protein that interacts with and negatively modulates opioid receptor signalling. Previously, we showed that the δ-opioid receptor (δ-OR) forms a multiprotein signalling complex consisting of Gi/Go proteins and the Signal Transducer and Activator of Transcription 5B (STAT5B) that leads to neuronal differentiation and neurite outgrowth upon δ-ΟR activation. Here, we investigated whether RGS4 could participate in signalling pathways to regulate neurotropic events...
February 17, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28183734/skap2-is-required-for-%C3%AE-2-integrin-mediated-neutrophil-recruitment-and-functions
#3
Mark Boras, Stephanie Volmering, Arne Bokemeyer, Jan Rossaint, Helena Block, Bernadette Bardel, Veerle Van Marck, Barbara Heitplatz, Stefanie Kliche, Annegret Reinhold, Clifford Lowell, Alexander Zarbock
Integrin activation is required for neutrophil functions. Impaired integrin activation on neutrophils is the hallmark of leukocyte adhesion deficiency (LAD) syndrome in humans, characterized by impaired leukocyte recruitment and recurrent infections. The Src kinase-associated phosphoprotein 2 (Skap2) is involved in integrin functions in different leukocyte subtypes. However, the role of Skap2 in β2 integrin activation and neutrophil recruitment is unknown. In this study, we demonstrate the crucial role of Skap2 in regulating actin polymerization and binding of talin-1 and kindlin-3 to the β2 integrin cytoplasmic domain, thereby being indispensable for β2 integrin activation and neutrophil recruitment...
February 9, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28179641/shank-proteins-roles-at-the-synapse-and-in-autism-spectrum-disorder
#4
REVIEW
Patricia Monteiro, Guoping Feng
Several large-scale genomic studies have supported an association between cases of autism spectrum disorder and mutations in the genes SH3 and multiple ankyrin repeat domains protein 1 (SHANK1), SHANK2 and SHANK3, which encode a family of postsynaptic scaffolding proteins that are present at glutamatergic synapses in the CNS. An evaluation of human genetic data, as well as of in vitro and in vivo animal model data, may allow us to understand how disruption of SHANK scaffolding proteins affects the structure and function of neural circuits and alters behaviour...
March 2017: Nature Reviews. Neuroscience
https://www.readbyqxmd.com/read/28156097/confinement-and-stabilization-of-fyn-sh3-folding-intermediate-mimetics-within-the-cavity-of-the-chaperonin-groel-demonstrated-by-relaxation-based-nmr
#5
David S Libich, Vitali Tugarinov, Rodolfo Ghirlando, G Marius Clore
The interaction of two folding intermediate mimetics of the model protein substrate Fyn SH3 with the chaperonin GroEL, a supramolecular foldase/unfoldase machine, has been investigated by (15)N relaxation-based nuclear magnetic resonance spectroscopy (lifetime line broadening, dark state exchange saturation transfer, and relaxation dispersion). The two mimetics comprise C-terminal truncations of wild-type and triple-mutant (A39V/N53P/V55L) Fyn SH3 in which the C-terminal strand of the SH3 domain is unfolded, while preserving the remaining domain structure...
February 8, 2017: Biochemistry
https://www.readbyqxmd.com/read/28138250/correlation-of-sash1-expression-and-ultrasonographic-features-in-breast-cancer
#6
Xuchu Gong, Jinna Wu, Jian Wu, Jun Liu, Hailin Gu, Hao Shen
OBJECTIVE: SASH1 is a member of the SH3/SAM adapter molecules family and has been identified as a new tumor suppressor and critical protein in signal transduction. An ectopic expression of SASH1 is associated with decreased cell viability of breast cancer. The aim of this study was to explore the association between SASH1 expression and the ultrasonographic features in breast cancer. PATIENTS AND METHODS: A total of 186 patients diagnosed with breast cancer were included in this study...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28127816/the-idl-of-e-coli-ssb-links-ssdna-and-protein-binding-by-mediating-protein-protein-interactions
#7
Piero R Bianco, Sasheen Pottinger, Hui Yin Tan, Trong Nguyenduc, Kervin Rex, Umesh Varshney
The E. coli single strand DNA binding protein (SSB) is essential to viability where it functions in two seemingly disparate roles: it binds to single stranded DNA (ssDNA) and to target proteins that comprise the SSB interactome. The link between these roles resides in a previously under-appreciated region of the protein known as the intrinsically disordered linker (IDL). We present a model wherein the IDL is responsible for mediating protein-protein interactions critical to each role. When interactions occur between SSB tetramers, cooperative binding to ssDNA results...
February 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28118077/midbody-localization-of-vinexin-recruits-rhotekin-to-facilitate-cytokinetic-abscission
#8
Yu-Wei Chang, Yi-Shuian Huang
Vinexin is a SH3 domain-containing adaptor protein that has diverse roles in cell adhesion, signal transduction, gene regulation and stress granule assembly. In this study, we found that vinexin localizes at the midbody during cell division and facilitates cytokinesis. Knockdown of vinexin in HeLa cells delayed the mitotic cell cycle progression and increased the time of cell abscission and the failure to resolve the cytoplasmic bridge. Midbody-localized vinexin is essential for recruiting rhotekin to this structure for cytokinesis because overexpression of a vinexin mutant without a rhotekin-binding motif or knockdown of rhotekin also impaired cytokinetic abscission and increased the number of cells arrested at the midbody stage...
January 24, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28112192/stac3-stably-interacts-through-its-c1-domain-with-cav1-1-in-skeletal-muscle-triads
#9
Marta Campiglio, Bernhard E Flucher
The adaptor protein STAC3 is essential for skeletal muscle excitation-contraction (EC) coupling and a mutation in the STAC3 gene has been linked to a severe muscle disease, Native American myopathy (NAM). However the function of STAC3, its interaction partner, and the mode of interaction within the EC-coupling complex remained elusive. Here we demonstrate that STAC3 forms a stable interaction with the voltage-sensor of EC-coupling, CaV1.1, and that this interaction depends on a hitherto unidentified protein-protein binding pocket in the C1 domain of STAC3...
January 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28111446/functional-analysis-of-sh3-domain-containing-ring-finger-2-sh3rf2-during-the-myogenic-differentiation-of-qm7-cells
#10
Si Won Kim, Jeong Hyo Lee, Tae Sub Park
Objective: Owing to the public availability of complete genome sequences, including avian species, massive bioinformatics analyses may be conducted for computational gene prediction and the identification of gene regulatory networks through various informatics tools. However, to evaluate the biofunctional activity of a predicted target gene, in vivo and in vitro functional genomic analyses should be a prerequisite. Methods: Due to a lack of quail genomic sequence information, we first identified the partial genomic structure and sequences of the quail SH3 domain containing ring finger 2 (SH3RF2) gene...
December 27, 2016: Asian-Australasian Journal of Animal Sciences
https://www.readbyqxmd.com/read/28111343/thermodynamic-contribution-of-backbone-conformational-entropy-in-the-binding-between-sh3-domain-and-proline-rich-motif
#11
Danyun Zeng, Qingliang Shen, Jae-Hyun Cho
Biological functions of intrinsically disordered proteins (IDPs), and proteins containing intrinsically disordered regions (IDRs) are often mediated by short linear motifs, like proline-rich motifs (PRMs). Upon binding to their target proteins, IDPs undergo a disorder-to-order transition which is accompanied by a large conformational entropy penalty. Hence, the molecular mechanisms underlying control of conformational entropy are critical for understanding the binding affinity and selectivity of IDPs-mediated protein-protein interactions (PPIs)...
January 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28106985/transparent-window-vibrational-probes-for-the-characterization-of-proteins-with-high-structural-and-temporal-resolution
#12
Ramkrishna Adhikary, Jörg Zimmermann, Floyd E Romesberg
Vibrational spectroscopy provides a direct route to the physicochemical characterization of molecules. While both IR and Raman spectroscopy have been used for decades to provide detailed characterizations of small molecules, similar studies with proteins are largely precluded due to spectral congestion. However, the vibrational spectra of proteins do include a "transparent window", between ∼1800 and ∼2500 cm(-1), and progress is now being made to develop site-specifically incorporated carbon-deuterium (C-D), cyano (CN), thiocyanate (SCN), and azide (N3) "transparent window vibrational probes" that absorb within this window and report on their environment to facilitate the characterization of proteins with small molecule-like detail...
January 20, 2017: Chemical Reviews
https://www.readbyqxmd.com/read/28105185/lim-and-sh3-protein-1-promotes-tumor-proliferation-and-metastasis-in-lung-carcinoma
#13
Xueqiong Lin, Xianhui Liu, Yusen Fang, Xuefen Weng
Lung cancer is the most frequently diagnosed cancer and the leading cause of cancer-related mortality worldwide. In the present study, we focused on LIM and SH3 protein 1 (LASP-1), a key molecule involved in the development of multiple cancers, and attempted to elucidate its effect on the oncogenesis of lung cancer. We determined the expression level of LASP-1 in lung cancer using reverse transcription-quantitative polymerase chain reaction and western blot analysis, and also studied the potential function of LASP-1 in lung cancer cell growth, apoptosis and migration by small interfering RNA transfection...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28105178/prognostic-relevance-of-samsn1-expression-in-gastric-cancer
#14
Mitsuro Kanda, Dai Shimizu, Satoshi Sueoka, Shuji Nomoto, Hisaharu Oya, Hideki Takami, Kazuhiro Ezaka, Ryoji Hashimoto, Yuri Tanaka, Daisuke Kobayashi, Chie Tanaka, Suguru Yamada, Tsutomu Fujii, Goro Nakayama, Hiroyuki Sugimoto, Masahiko Koike, Michitaka Fujiwara, Yasuhiro Kodera
The prognosis for patients with advanced gastric cancer (GC) remains poor. The identification of biomarkers relevant to the recurrence and metastasis of GC is advantageous for stratifying patients and proposing novel molecular targets. In the present study the oncological roles of SAM domain, SH3 domain and nuclear localization signals 1 (SAMSN1), a mediator of B-cell function, were elucidated in GC. The expression and methylation status of SAMSN1 were investigated in a panel of 11 GC cell lines. Immunohistochemical staining was performed to determine the pattern of SAMSN1 protein expression in gastric tissues...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28104453/alphavirus-polymerase-and-rna-replication
#15
REVIEW
Maija K Pietilä, Kirsi Hellström, Tero Ahola
Alphaviruses are typically arthropod-borne, and many are important pathogens such as chikungunya virus. Alphaviruses encode four nonstructural proteins (nsP1-4), initially produced as a polyprotein P1234. nsP4 is the core RNA-dependent RNA polymerase but all four nsPs are required for RNA synthesis. The early replication complex (RC) formed by the polyprotein P123 and nsP4 synthesizes minus RNA strands, and the late RC composed of fully processed nsP1-nsP4 is responsible for the production of genomic and subgenomic plus strands...
January 16, 2017: Virus Research
https://www.readbyqxmd.com/read/28104445/the-sh3-domain-of-caskin1-binds-to-lysophosphatidic-acid-suggesting-a-direct-role-for-the-lipid-in-intracellular-signaling
#16
Kitti Koprivanacz, Orsolya Tőke, Balázs Besztercei, Tünde Juhász, László Radnai, Balázs Merő, Judith Mihály, Mária Péter, Gábor Balogh, László Vígh, László Buday, Károly Liliom
Src homology 3 or SH3 domains constitute one of the most common protein domains in signal transduction, generally characterized by their binding to proline-rich sequences on interacting signaling proteins. Caskin1, a scaffold protein regulating cortical actin filaments, enriched in neural synapses in mammals, has an atypical SH3 domain. Key aromatic residues necessary for ligand binding that are present in canonical SH3 domains are missing from Caskin1 SH3. In concordance, proline-rich interacting partner could not be identified yet...
January 16, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28101242/screening-and-analysis-of-breast-cancer-genes-regulated-by-the-human-mammary-microenvironment-in-a-humanized-mouse-model
#17
Mingjie Zheng, Jue Wang, Lijun Ling, Dandan Xue, Shui Wang, Yi Zhao
Tumor microenvironments play critical regulatory roles in tumor growth. Although mouse cancer models have contributed to the understanding of human tumor biology, the effectiveness of mouse cancer models is limited by the inability of the models to accurately present humanized tumor microenvironments. Previously, a humanized breast cancer model in severe combined immunodeficiency mice was established, in which human breast cancer tissue was implanted subcutaneously, followed by injection of human breast cancer cells...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28096337/stress-granule-associated-protein-g3bp2-regulates-breast-tumor-initiation
#18
Nisha Gupta, Mark Badeaux, Yiqian Liu, Kamila Naxerova, Dennis Sgroi, Lance L Munn, Rakesh K Jain, Igor Garkavtsev
Breast tumors contain tumorigenic cancer cells, termed "tumor-initiating cells" (TICs), which are capable of both replenishing themselves and giving rise to populations of nontumorigenic breast cancer cells (non-TICs). However, the molecular mechanisms responsible for breast tumor initiation remain poorly understood. Here we describe a chemical screening strategy to identify small molecules that enhance the effect of chemotherapeutic agents on TIC-enriched breast cancer cells. We identified proteins that interact with the lead compound C108, including the stress granule-associated protein, GTPase-activating protein (SH3 domain)-binding protein 2, G3BP2...
January 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28078722/ssb-and-the-recg-dna-helicase-an-intimate-association-to-rescue-a-stalled-replication-fork
#19
REVIEW
Piero R Bianco, Yuri L Lyubchenko
In E. coli, the regression of stalled DNA replication forks is catalyzed by the DNA helicase RecG. One means of gaining access to the fork is by binding to the single strand binding protein or SSB. This interaction occurs via the wedge domain of RecG and the intrinsically disordered linker (IDL) of SSB, in a manner similar to that of SH3 domains binding to PXXP motif-containing ligands in eukaryotic cells. During loading, SSB remodels the wedge domain so that the helicase domains bind to the parental, duplex DNA, permitting the helicase to translocate using thermal energy...
January 12, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28067252/two-step-amyloid-aggregation-sequential-lag-phase-intermediates
#20
Fabio Castello, Jose M Paredes, Maria J Ruedas-Rama, Miguel Martin, Mar Roldan, Salvador Casares, Angel Orte
The self-assembly of proteins into fibrillar structures called amyloid fibrils underlies the onset and symptoms of neurodegenerative diseases, such as Alzheimer's and Parkinson's. However, the molecular basis and mechanism of amyloid aggregation are not completely understood. For many amyloidogenic proteins, certain oligomeric intermediates that form in the early aggregation phase appear to be the principal cause of cellular toxicity. Recent computational studies have suggested the importance of nonspecific interactions for the initiation of the oligomerization process prior to the structural conversion steps and template seeding, particularly at low protein concentrations...
January 9, 2017: Scientific Reports
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