Signal transduction pathways mediated by colony stimulating factor-1 receptor

Colony-stimulating factor-1 (CSF-1), which is necessary for cell proliferation and differentiation, regulates both immediate and delayed early responses throughout G1 phase. The binding of CSF-1 to its receptor (CSF-1R) triggers phosphorylation of the receptor and its intrinsic tyrosine kinase. The activated receptor binds directly to cytoplasmic effector proteins, which induce multiple-signal transduction pathways. CSF-1 can induce the c-myc gene expression via Ras and Ets-related proteins. The expression of c-fos/jun family genes is also targeted following the activation of Ras. CSF-1R activates STAT1 and STAT3 to participate in signaling, but JAKs do not appear to contribute to signaling by CSF-1R. CSF-1R activates PI3-kinase, and PI3-ki can interact with downstream proteins by the MAPKK-related pathway independent of Ras/Raf. PC-PLC can enforce signaling in response to CSF-1. Furthermore, the turnover and dephosphorylation by the phosphatase SHPTP1 of CSF-1R are the major mechanism in the negative regulation of signaling by CSF-1R     

Search for new antiphytovirucides

The lead compound of substituted 2-(4′-hydroxyphenyl)benzimidazoles were modified by phosphorylation sulfonation and carboxymethylation. The benzimidazoloamidophosphate (6) (7) have better activity against tobacco mosaic virus (TMV). The benzimidazolophenoxyacetic acid, phenoxysulfonic acid containing trifluoromethyl, and nitro group have 77%≈85% efficiency for wheat rust disease. Supported by the National Natural Science Foundation of China and National Laboratory of Elemento Organic Chemistry Nankai University Qu Fanqi: born in 1952, Associate professor     

植物中钙解码机制的研究进展

Ca2＋作为重要的第二信使,在植物生长发育中起着非常重要的作用．目前已经鉴定的植物Ca2＋传感器蛋白有：钙调素（CaM）、类钙调素蛋白（CMLs）、钙依赖型蛋白激酶（CDPKs）和类钙调磷酸酶B亚基蛋白（CBLs）及其互作蛋白激酶（CIPKs）,这些传感器蛋白多以基因家族形式存在,并且在植物中能够形成错综复杂的钙离子信号传递网络系统．主要从植物Ca2＋传感器蛋白的生化特性、生理功能和靶蛋白3个方面,综述了植物解码钙信号机制的最新研究进展．     

含氧化膦结构半芳香聚酰胺的合成与表征

以含磷芳香二胺双(3–氨基苯基)苯基氧化膦(BAPPO)和己二酸为单体,通过Yamazaki膦酰化反应制备新型半芳香聚酰胺(PA6I).研究反应温度、单体浓度、溶剂体系以及反应时间对聚合物特性黏度的影响,得到特性黏度为0.47,dL/g的聚合物.利用傅里叶变换红外光谱(FTIR)、核磁共振谱(1H,NMR)对含磷半芳香聚酰胺进行结构表征;利用差示扫描量热法(DSC)和热重分析(TGA)研究新型半芳香聚酰胺的热性能.结果表明聚合物具有优良的热性能,Tg为206,℃,5%热分解温度为388.1,℃.薄膜样品的极限氧指数为43%,表明该聚合物有优良的阻燃性.     

Phytanic acid impairs mitochondrial respiration through protonophoric action

Refsum disease is a rare, inherited neurodegenerative disorder characterized by accumulation of the dietary branched-chain fatty acid phytanic acid in plasma and tissues caused by a defect in the alphaoxidation pathway. The accumulation of phytanic acid is believed to be the main pathophysiological cause of the disease. However, the exact mechanism(s) by which phytanic acid exerts its toxicity have not been resolved. In this study, the effect of phytanic acid on mitochondrial respiration was investigated. The results show that in digitonin-permeabilized fibroblasts, phytanic acid decreases ATP synthesis, whereas substrate oxidation per se is not affected. Importantly, studies in intact fibroblasts revealed that phytanic acid decreases both the mitochondrial membrane potential and NAD(P)H autofluorescence. Taken together, the results described here show that unesterified phytanic acid exerts its toxic effect mainly through its protonophoric action, at least in human skin fibroblasts. Received 4 August 2007; received after revision 26 September 2007; accepted 10 October 2007 J. C. Komen, F. Distelmaier: These authors contributed equally to this work.     

Serine/threonine protein phosphatases in DNA damage response

DNA damage response (DDR) is among the most important of the mechanisms that maintain genome stability which, when destabilized, predisposes organs to cancer. Reversible phosphorylation mediated by protein kinases and protein phosphatases regulates most, if not all, cellular activities, including DDR. Protein kinase inhibitors have become the main focus of targeted therapy and anticancer drug development. However, our limited knowledge of protein phosphatase function is compromising our capacity to develop therapeutic agents against phosphatases. In this review, we summarize the roles of serine/threonine protein phosphatases involved in DDR and propose that in situ dephosphorylation of phosphoproteins by protein phosphatases, instead of proteasome-mediated degradation of phosphoproteins, is mainly employed by cells.     

Myelin basic protein: a multifunctional protein

Myelin basic protein (MBP), the second most abundant protein in central nervous system myelin, is responsible for adhesion of the cytosolic surfaces of multilayered compact myelin. A member of the ‘intrinsically disordered’ or conformationally adaptable protein family, it also appears to have several other functions. It can interact with a number of polyanionic proteins including actin, tubulin, Ca²⁺-calmodulin, and clathrin, and negatively charged lipids, and acquires structure on binding to them. It may act as a membrane actin-binding protein, which might allow it to participate in transmission of extracellular signals to the cytoskeleton in oligodendrocytes and tight junctions in myelin. Some size isoforms of MBP are transported into the nucleus and thus they may also bind polynucleotides. Extracellular signals received by myelin or cultured oligodendrocytes cause changes in phosphorylation of MBP, suggesting that MBP is also involved in signaling. Further study of this very abundant protein will reveal how it is utilized by the oligodendrocyte and myelin for different purposes. Received 2 March 2006; received after revision 12 April 2006; accepted 16 May 2006     

Optimization of the cellular import of functionally active SH2-domain-interacting phosphopeptides

Phosphopeptides interacting with src homology 2 (SH2) domains can activate essential signaling enzymes in vitro. When delivered to cells, they may disrupt protein-protein interactions, thereby influencing intracellular signaling. We showed earlier that phosphopeptides corresponding to the inhibitory motif of Fcγ receptor IIb and a motif of the Grb2-associated binder 1 adaptor protein activate SH2-containing tyrosine phosphatase 2 in vitro. To study the ex vivo effects of these peptides, we have now compared different methods for peptide delivery: (i) permeabilization of the target cells and (ii) the use of cell-permeable vectors, which are potentially able to transport biologically active compounds into B cells. We found octanoyl-Arg₈ to be an optimal carrier for the delivery of phosphopeptides to the cells. With this strategy, the function of cell-permeable SHP-2-binding phosphopeptides was analyzed. These peptides modulated the protein phosphorylation in B cells in a dose- and time-dependent manner. Received 27 July 2006; received after revision 4 September 2006; accepted 18 September 2006     

视网膜母细胞瘤基因产物磷酸化水平与细胞生长状态的关系

随着无血清培养细胞时间的延长，红胞合成Ｒｂ蛋白量和磷酸化水平逐渐降低，当细胞生长停止时，Ｒｂ蛋白处于低磷外化状态．正丁酸钠可诱导ＨＬ６０终端分化为单核－巨噬细胞；视黄酸、二甲基亚砜使ＨＬ６０分化为粒细胞．尽管分化途径不同．但是终端分化的细胞都只能合成低磷酸化的Ｒｂ蛋白．结果表明当细胞处于生长停滞状态，细胞都只能合成低磷酸化的Ｒｂ蛋白．