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11.
Rapid Plasma Membrane Anchoring of Newly Synthesized p59 fyn: Selective Requirement for NH2-Terminal Myristoylation and Palmitoylation at Cysteine-3 下载免费PDF全文
The trafficking of Src family proteins after biosynthesis is poorly defined. Here we studied the role of dual fatty acylation with myristate and palmitate in biosynthetic transport of p59fyn. Metabolic labeling of transfected COS or NIH 3T3 cells with [35S]methionine followed by analysis of cytosolic and total membrane fractions showed that Fyn became membrane bound within 5 min after biosynthesis. Newly synthesized Src, however, accumulated in the membranes between 20– 60 min. Northern blotting detected Fyn mRNA specifically in soluble polyribosomes and soluble Fyn protein was only detected shortly (1–2 min) after radiolabeling. Use of chimeric Fyn and Src constructs showed that rapid membrane targeting was mediated by the myristoylated NH2-terminal sequence of Fyn and that a cysteine at position 3, but not 6, was essential. Examination of Gαo-, Gαs-, or GAP43-Fyn fusion constructs indicated that rapid membrane anchoring is exclusively conferred by the combination of N-myristoylation plus palmitoylation of cysteine-3. Density gradient analysis colocalized newly synthesized Fyn with plasma membranes. Interestingly, a 10–20-min lag phase was observed between plasma membrane binding and the acquisition of non-ionic detergent insolubility. We propose a model in which synthesis and myristoylation of Fyn occurs on soluble ribosomes, followed by rapid palmitoylation and plasma membrane anchoring, and a slower partitioning into detergent-insoluble membrane subdomains. These results serve to define a novel trafficking pathway for Src family proteins that are regulated by dual fatty acylation. 相似文献
12.
In an attempt to determine whether phagocytosis of collagen by fibroblasts involves binding of the fibril to the plasma membrane, the effect of the lectin concanavalin A (Con A) was studied in an in vitro model system. Metacarpal bone rudiments from 19-day-old mouse fetuses were incubated with varying concentrations of the lectin. Quantitative electron microscopic analysis indicated that Con A caused a dose-related increase in the amount of phagocytosed collagen fibrils in periosteal fibroblasts, suggesting either an enhanced uptake or a decreased intracellular breakdown of fibrils. Since a Con A-inducible increase was not seen in the combined presence of both the lectin and the proteinase inhibitor leupeptin, which is known to inhibit the intracellular digestion of phagocytosed fibrillar collagen, it is unlikely that Con A stimulated phagocytosis. Based on the finding that Con A interfered with the digestion of a synthetic substrate by the collagenolytic lysosomal enzyme cathepsin B it is suggested that the augmentation of intracellular fibrillar collagen under the influence of the lectin was due to a decreased intracellular digestion. Since Con A did not inhibit the uptake of collagen fibrils by the fibroblasts it is concluded that Con A-inhibitable binding sites for collagen molecules are unlikely to be involved in phagocytosis of collagen fibrils by fibroblasts. 相似文献
13.
Inclusion of IAA in the vase water had little effect on leaf yellowing in cut flowering branches of Alstroemeria pelegrina L. while kinetin delayed leaf yellowing at 10-4M (continuous treatment). Chlorophyll was effectively retained by 10-7M gibberellic acid (GA) in the vase water or by a 20h pulse at 5°C with 10-5/10-4M GA. After 16h of 14C-GA, uptake at 20°C relatively high levels of 14C were found in leaves and low levels in stems and flowers. After this treatment about half of the 14C-GA, in leaves was metabolized into unknown compounds.
Corrigendum. Owing to an error in the proofreading process, the article was published incorrectly. The article as it should have been published is presented here. 相似文献
14.
Johannes Boonstra Paul T. Van Der Saag Wouter H. Moolenaar Siegfried W. De Laat 《Experimental cell research》1981,131(2):452-455
Nerve growth factor (NGF) induces neuronal differentiation of rat pheochromocytoma cells (PC12). Here we show that NGF causes a stimulation of Na+,K+-pump mediated K+ influx, with a maximum at 30 min after addition of NGF. The stimulation of the Na+,K+-pump is completely blocked by the Na+-flux inhibitor amiloride (0.2 mM) and can be mimicked by the Na+ ionophore monensin. These results suggest that NGF causes a rapid enhancement of Na+ influx leading to an activation of the Na+,K+-pump, a mechanism similar to the action of other growth factors. 相似文献
15.
16.
Temmink Ralph J. M. Dorenbosch Martijn Lamers Leon P. M. Smolders Alfons J. P. Rip Winnie Lengkeek Wouter Didderen Karin Fivash Gregory S. Bouma Tjeerd J. van der Heide Tjisse 《Hydrobiologia》2021,848(17):3987-3999
Hydrobiologia - Aquatic ecosystems provide vital services, and macrophytes play a critical role in their functioning. Conceptual models indicate that in shallow lakes, plants with different growth... 相似文献
17.
Tan Laura X. L. van Dongen Wouter F. D. Sherman Craig D. H. Ekanayake Kasun B. Dann Peter Sutherland Duncan R. Weston Michael A. 《Biological invasions》2021,23(8):2485-2487
Biological Invasions - A correction to this paper has been published: https://doi.org/10.1007/s10530-021-02548-x 相似文献
18.
Wouter de Munter Arjen B Blom Monique M Helsen Birgitte Walgreen Peter M van der Kraan Leo AB Joosten Wim B van den Berg Peter LEM van Lent 《Arthritis research & therapy》2013,15(6):R178
Introduction
Osteoarthritis (OA) is associated with the metabolic syndrome, however the underlying mechanisms remain unclear. We investigated whether low density lipoprotein (LDL) accumulation leads to increased LDL uptake by synovial macrophages and affects synovial activation, cartilage destruction and enthesophyte/osteophyte formation during experimental OA in mice.Methods
LDL receptor deficient (LDLr−/−) mice and wild type (WT) controls received a cholesterol-rich or control diet for 120 days. Experimental OA was induced by intra-articular injection of collagenase twelve weeks after start of the diet. OA knee joints and synovial wash-outs were analyzed for OA-related changes. Murine bone marrow derived macrophages were stimulated with oxidized LDL (oxLDL), whereupon growth factor presence and gene expression were analyzed.Results
A cholesterol-rich diet increased apolipoprotein B (ApoB) accumulation in synovial macrophages. Although increased LDL levels did not enhance thickening of the synovial lining, S100A8 expression within macrophages was increased in WT mice after receiving a cholesterol-rich diet, reflecting an elevated activation status. Both a cholesterol-rich diet and LDLr deficiency had no effect on cartilage damage; in contrast, ectopic bone formation was increased within joint ligaments (fold increase 6.7 and 6.1, respectively). Moreover, increased osteophyte size was found at the margins of the tibial plateau (4.4 fold increase after a cholesterol-rich diet and 5.3 fold increase in LDLr−/− mice). Synovial wash-outs of LDLr−/− mice and supernatants of macrophages stimulated with oxLDL led to increased transforming growth factor-beta (TGF-β) signaling compared to controls.Conclusions
LDL accumulation within synovial lining cells leads to increased activation of synovium and osteophyte formation in experimental OA. OxLDL uptake by macrophages activates growth factors of the TGF-superfamily. 相似文献19.
Kirsi A. Virtanen Wouter D. van Marken Lichtenbelt Pirjo Nuutila 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2013,1831(5):1004-1008
Human adults have functionally active BAT. The metabolic function can be reliably measured in vivo using modern imaging modalities (namely PET/CT). Cold seems to be one of the most potent stimulators of BAT metabolic activity but other stimulators (for example insulin) are actively studied. Obesity is related to lower metabolic activity of BAT but it may be reversed after successful weight reduction such as after bariatric surgery. This article is part of a Special Issue entitled Brown and White Fat: From Signaling to Disease. 相似文献
20.
Angela Helfricht Wouter W Wiegant Peter E Thijssen Alfred C Vertegaal Martijn S Luijsterburg Haico van Attikum 《Cell cycle (Georgetown, Tex.)》2013,12(18):3070-3082
The cellular response to ionizing radiation (IR)-induced DNA double-strand breaks (DSBs) in native chromatin requires a tight coordination between the activities of DNA repair machineries and factors that modulate chromatin structure. SMARCA5 is an ATPase of the SNF2 family of chromatin remodeling factors that has recently been implicated in the DSB response. It forms distinct chromatin remodeling complexes with several non-canonical subunits, including the remodeling and spacing factor 1 (RSF1) protein. Despite the fact that RSF1 is often overexpressed in tumors and linked to tumorigenesis and genome instability, its role in the DSB response remains largely unclear. Here we show that RSF1 accumulates at DSB sites and protects human cells against IR-induced DSBs by promoting repair of these lesions through homologous recombination (HR) and non-homologous end-joining (NHEJ). Although SMARCA5 regulates the RNF168-dependent ubiquitin response that targets BRCA1 to DSBs, we found RSF1 to be dispensable for this process. Conversely, we found that RSF1 facilitates the assembly of centromere proteins CENP-S and CENP-X at sites of DNA damage, while SMARCA5 was not required for these events. Mechanistically, we uncovered that CENP-S and CENP-X, upon their incorporation by RSF1, promote assembly of the NHEJ factor XRCC4 at damaged chromatin. In contrast, CENP-S and CENP-X were dispensable for HR, suggesting that RSF1 regulates HR independently of these centromere proteins. Our findings reveal distinct functions of RSF1 in the 2 major pathways of DSB repair and explain how RSF1, through the loading of centromere proteins and XRCC4 at DSBs, promotes repair by non-homologous end-joining. 相似文献