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排序方式: 共有630条查询结果,搜索用时 15 毫秒
121.
Newell AE Fiedler SE Ruan JM Pan J Wang PJ Deininger J Corless CL Carr DW 《Cell motility and the cytoskeleton》2008,65(7):539-552
A-kinase anchoring proteins (AKAPs) bind to protein kinase A (PKA) via an amphipathic helix domain that interacts with a dimerization/docking domain on the regulatory (R) subunit of PKA. Four other mammalian proteins (ROPN1, ASP, SP17, and CABYR) also contain a highly conserved RII dimerization/docking (R2D2) domain, suggesting all four proteins may interact with all AKAPs in a manner similar to RII. All four of these proteins were originally detected in the flagellum of mammalian sperm. In this report, we demonstrate that all four R2D2 proteins are expressed in a wide variety of tissues and three of the proteins SP17, CABYR, and ASP are located in motile cilia of human bronchus and fallopian tubes. In addition, we detect SP17 in primary cilia. We also provide evidence that ROPN1 and ASP bind to a variety of AKAPs and this interaction can be disrupted with anchoring inhibitor peptides. The interaction of SP17 and CABYR with AKAPs appears to be much more limited. None of the R2D2 proteins appears to bind cAMP, a fundamental characteristic of the regulatory subunits of PKA. These observations suggest that R2D2 proteins utilize docking interactions with AKAPs to accomplish their function of regulating cilia and flagella. Based on location, affinity for AKAPs and lack of affinity for cAMP, it appears that each R2D2 protein has a unique role in this process. 相似文献
122.
123.
Background
Protein translocation across the membrane of the Endoplasmic Reticulum (ER) is the first step in the biogenesis of secretory and membrane proteins. Proteins enter the ER by the Sec61 translocon, a proteinaceous channel composed of three subunits, α, β and γ. While it is known that Sec61α forms the actual channel, the function of the other two subunits remains to be characterized.Results
In the present study we have investigated the function of Sec61β in Drosophila melanogaster. We describe its role in the plasma membrane traffic of Gurken, the ligand for the Epidermal Growth Factor (EGF) receptor in the oocyte. Germline clones of the mutant allele of Sec61β show normal translocation of Gurken into the ER and transport to the Golgi complex, but further traffic to the plasma membrane is impeded. The defect in plasma membrane traffic due to absence of Sec61β is specific for Gurken and is not due to a general trafficking defect.Conclusion
Based on our study we conclude that Sec61β, which is part of the ER protein translocation channel affects a post-ER step during Gurken trafficking to the plasma membrane. We propose an additional role of Sec61β beyond protein translocation into the ER. 相似文献124.
Lorna R Fiedler 《Cell Adhesion & Migration》2009,3(2):143-145
Rac1 is a member of the small Rho GTPase family, which controls actin cytoskeleton and focal adhesion dynamics in cellular protrusions. While Rac1 therefore contributes to regulation of endothelial cell-cell and cell-matrix interactions, a detailed understanding of its role in endothelium function is lacking. Recently, the role of Rac1 in development and postnatal regulation of the cardiovascular system has been investigated in murine models lacking Rac1 specifically in endothelium. Homozygous endothelial deletion was lethal, primarily due to defects in angiogenesis. Rac1-deficient endothelial cells were unable to form cellular protrusions/lamellipodia, leading to impaired cell-cell and cell-matrix interactions, and resulting in dysfunctional adhesion, motility, permeability and capillary morphogenesis. Development was normal in the heterozygous model, however a hypertensive phenotype was observed as a result of reduced nitric oxide signalling. Nitric oxide synthase activity was regulated by Rac1 at multiple levels; expression, mRNA stability and uptake of the nitric oxide synthase substrate L-arginine. Therefore, Rac1 activity is essential in regulating developmental and postnatal angiogenesis and cardiovascular function, by controlling nitric oxide production, and formation of endothelial cell protrusions.Key words: Rac1, angiogenesis, endothelial, motility, lamellipodia, nitric oxide, nitric oxide synthase 相似文献
125.
Fiedler B Feil R Hofmann F Willenbockel C Drexler H Smolenski A Lohmann SM Wollert KC 《The Journal of biological chemistry》2006,281(43):32831-32840
Cardiac myocyte apoptosis during ischemia and reperfusion (I/R) is tightly controlled by a complex network of stress-responsive signaling pathways. One pro-apoptotic pathway involves the interaction of the scaffold protein TAB1 with p38 mitogen-activated protein kinase (p38 MAPK) leading to the autophosphorylation and activation of p38 MAPK. Conversely, NO and its second messenger cGMP protect cardiac myocytes from apoptosis during I/R. We provide evidence that the cGMP target cGMP-dependent protein kinase type I (PKG I) interferes with TAB1-p38 MAPK signaling to protect cardiac myocytes from I/R injury. In isolated neonatal cardiac myocytes, activation of PKG I inhibited the interaction of TAB1 with p38 MAPK, p38 MAPK phosphorylation, and apoptosis induced by simulated I/R. During I/R in vivo, mice with a cardiac myocyte-restricted deletion of PKG I displayed a more pronounced interaction of TAB1 with p38 MAPK and a stronger phosphorylation of p38 MAPK in the myocardial area at risk during reperfusion and more apoptotic cardiac myocytes in the infarct border zone as compared with wild-type littermates. Notably, adenoviral expression of a constitutively active PKG I mutant truncated at the N terminus(PKGI-DeltaN1-92) did not inhibit p38 MAPK phosphorylation and apoptosis induced by simulated I/R in vitro, indicating that the N terminus of PKG I is required. As shown by co-immunoprecipitation experiments in HEK293 cells, cGMP-activated PKG I, but not constitutively active PKG I-DeltaN1-92 or PKG I mutants carrying point mutations in the N-terminal leucine-isoleucine zipper, interacted with p38 MAPK, and prevented the binding of TAB1 to p38 MAPK. Together, our data identify a novel interaction between the cGMP target PKG I and the TAB1-p38 MAPK signaling pathway that serves as a defense mechanism against myocardial I/R injury. 相似文献
126.
Elevational species richness gradients in a hyperdiverse insect taxon: a global meta‐study on geometrid moths 下载免费PDF全文
Jan Beck Christy M. McCain Jan C. Axmacher Louise A. Ashton Florian Bärtschi Gunnar Brehm Sei‐Woong Choi Oldrich Cizek Robert K. Colwell Konrad Fiedler Cristina L. Francois Steven Highland Jeremy D. Holloway Jurie Intachat Tomas Kadlec Roger L. Kitching Sarah C. Maunsell Thomas Merckx Akihiro Nakamura Erica Odell Weiguo Sang Pagi S. Toko Jaroslav Zamecnik Yi Zou Vojtech Novotny 《Global Ecology and Biogeography》2017,26(4):412-424
127.
Heinrich Eder Wolfgang Fiedler Xaver Pascoe 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2011,197(1):109-117
Primary feathers of soaring land birds have evolved into highly specialized flight feathers characterized by morphological
improvements affecting aerodynamic performance. The foremost feathers in the cascade have to bear high lift-loading with a
strong bending during soaring flight. A challenge to the study of feather aerodynamics is to understand how the observed low
drag and high lift values in the Reynolds (Re) regime from 1.0 to 2.0E4 can be achieved. Computed micro-tomography images show that the feather responds to high lift-loading
with an increasing nose-droop and profile-camber. Wind-tunnel tests conducted with the foremost primary feather of a White
Stork (Ciconia ciconia) at Re = 1.8E4 indicated a surprisingly high maximum lift coefficient of 1.5 and a glide ratio of nearly 10. We present evidence
that this is due to morphologic characteristics formed by the cristae dorsales as well as air-permeable arrays along the rhachis. Measurements of lift and drag forces with open and closed pores confirmed the efficiency of this mechanism. Porous structures
facilitate a blow out, comparable to technical blow-hole turbulators for sailplanes and low speed turbine-blades. From our
findings, we conclude that the mechanism has evolved in order to affect the boundary layer and to reduce aerodynamic drag
of the feather. 相似文献
128.
Siemens N Patenge N Otto J Fiedler T Kreikemeyer B 《The Journal of biological chemistry》2011,286(24):21612-21622
The entry into epithelial cells and the prevention of primary immune responses are a prerequisite for a successful colonization and subsequent infection of the human host by Streptococcus pyogenes (group A streptococci, GAS). Here, we demonstrate that interaction of GAS with plasminogen promotes an integrin-mediated internalization of the bacteria into keratinocytes, which is independent from the serine protease activity of potentially generated plasmin. α(1)β(1)- and α(5)β(1)-integrins were identified as the major keratinocyte receptors involved in this process. Inhibition of integrin-linked kinase (ILK) expression by siRNA silencing or blocking of PI3K and Akt with specific inhibitors, reduced the GAS M49-plasminogen/plasmin-mediated invasion of keratinocytes. In addition, blocking of actin polymerization significantly reduced GAS internalization into keratinocytes. Altogether, these results provide a first model of plasminogen-mediated GAS invasion into keratinocytes. Furthermore, we demonstrate that plasminogen binding protects the bacteria against macrophage killing. 相似文献
129.
Kuzmenko ES Djafarzadeh S Cakar ZP Fiedler K 《The international journal of biochemistry & cell biology》2004,36(3):519-534
Endothelial cell (EC) cultures of different, selected vascular beds and/or organs were screened for receptor-mediated transport of proteins with a semipermeable filter assay. In SVEC4-10 cells, a mouse lymphoid endothelial cell line, orosomucoid, albumin, insulin and LDL were transcytosed from the apical (luminal) to basal (abluminal) side by a receptor-mediated pathway. Specific LDL transcytosis involved transport of intact LDL. A pathway of degradation of LDL and basal release involved vesicles in transport to lysosomes and amino acid merocrine secretion. This newly described transcellular passage of LDL via lysosomes, as well as the standard pathway, were reduced to 70% by PEG(50)-cholesterol (PEG-Chol). Combined results of temperature-dependence analysis and PEG(50)-cholesterol sensitivity show that two pathways contribute to general LDL transcellular passage. We suggest a mechanism of domain hopping by protein membrane diffusion of receptors as the pathway for intact LDL delivery. Based on theoretical considerations we propose that active transport by protein membrane diffusion can be facilitated by an organizational structure of lipid microdomains and polar cellular organization. 相似文献
130.
Dubowchik GM Michne JA Zuev D Schwartz W Scola PM James CA Ruediger EH Pin SS Burris KD Balanda LA Gao Q Wu D Fung L Fiedler T Browman KE Taber MT Zhang J 《Bioorganic & medicinal chemistry letters》2003,13(22):3997-4000
2-arylamino-4-trifluoromethyl-5-aminomethylthiazoles represent a novel series of high-affinity corticotropin releasing factor-1 receptor (CRF(1)R) antagonists that are prepared in three steps in good overall yields. Herein, we report binding SAR as well as anxiolytic activity of an exemplary compound (7a, K(i)=8.6 nM) in a mouse canopy model. 相似文献