Signal transduction and regulation of translation initiation.

Regulation of the rate of protein synthesis is important in the control of cellular proliferation. Changes in the rate of protein translation are brought about primarily at the level of initiation, which is usually rate limiting. This regulation involves the reversible phosphorylation of key initiation factors. Translation initiation factors eIF-4F, eIF-4B, and ribosomal protein S6 are phosphorylated in response to a wide variety of mitogens, growth factors, and tyrosine kinase oncogenes. Thus, translation initiation factors are important components of signal transduction pathways activated by extracellular factors and oncogenes. Of particular interest is the messenger RNA 5' cap-binding protein, eIF-4E. Overexpression of eIF-4E in fibroblasts results in malignant transformation, suggesting that it is an important transducer of growth signals, and that aberrant expression of a translation factor can cause malignancy. Elucidation of the components of the signalling pathways which regulate initiation factor activity should increase our understanding of how extracellular factors and oncogenes effect cellular proliferation, and the role that translation plays in this process.     

Signal transduction and regulation of IbpreproHypSys in sweet potato

Hydroxyproline‐rich glycopeptides (HypSys) are small signalling peptides containing 18–20 amino acids. The expression of IbpreproHypSys, encoding the precursor of IbHypSys, was induced in sweet potato (Ipomoea batatas cv. Tainung 57) through wounding and IbHypSys treatments by using jasmonate and H₂O₂. Transgenic sweet potatoes overexpressing (OE) and silencing [RNA interference (RNAi)] IbpreproHypSys were created. The expression of the wound‐inducible gene for ipomoelin (IPO) in the local and systemic leaves of OE plants was stronger than the expression in wild‐type (WT) and RNAi plants after wounding. Furthermore, grafting experiments indicated that IPO expression was considerably higher in WT stocks receiving wounding signals from OE than from RNAi scions. However, wounding WT scions highly induced IPO expression in OE stocks. These results indicated that IbpreproHypSys expression contributed towards sending and receiving the systemic signals that induced IPO expression. Analysing the genes involved in the phenylpropanoid pathway demonstrated that lignin biosynthesis was activated after synthetic IbHypSys treatment. IbpreproHypSys expression in sweet potato suppressed Spodoptera litura growth. In conclusion, wounding induced the expression of IbpreproHypSys, whose protein product was processed into IbHypSys. IbHypSys stimulated IbpreproHypSys and IPO expression and enhanced lignin biosynthesis, thus protecting plants from insects.     

神经营养素信号转导研究进展

神经营养素（ＮＴｓ）与其膜受体相结合,促成ｔｒｋ同源二聚体的形成,激发Ｒａｓ信号转导途径,启动即早基因和延迟反应基因的转录,或直接参与各种生理反应。靶源性ＮＴｓ的作用由轴突末端ｔｒｋ受体介导,以磷酸化状态的ｔｒｋ或ＮＴ－ｔｒｋ复合物或被活化的其它信使分子等形式沿轴突逆行运输至胞浆胞核,实现其信号转导。ＮＴｓ的作用除了靶源性方式外,也存在局部的自分泌与旁分泌。损伤情况下,ＮＴｓ及其受体表达均增加,轴     

Cellular mechanisms of signal transduction for neurotrophins

The molecular cloning of new neuroactive growth factors and their receptors has greatly enhanced our understanding of important interactions among receptors and singnaling molecules. These studies have begun to illuminate some of the mechanisms that allow for specificity in neuronal signaling. Model cell systems, such as the PC-12 pheochromocytoma cell line, express receptors for these different neurotirophic factors, leading to comparisons of signaling pathways for these factors. Upon binding their ligands, these receptors undergo phosphorylation on tyrosine residues, which directs their interaction with signaling proteins containing src homology (SH2) domains, sequences that mediate associations with tyrosine-phosphorylated proteins. These SH2 proteins translate the tyrosine kinase activity of receptors into downstream events that result in the specific cellular response. Investigations such as these have revealed that molecular specificity in signaling pathways may arise from combinatorial diversity in interactions between receptors and key regulatory proteins.     

Signal transduction and virulence regulation in human and animal pathogens

Abstract Pathogens have developed many strategies for survival in animals and humans which possess very effective defense mechanisms. Although there are many different ways, in which pathogenic bacteria solved the problem to overcome the host defense, some common features of virulence mechanisms can be detected even in phylogenetically very distant bacteria (Finlay and Falkow (1989) Microb. Rev. 6 1375–1383). One important feature is that the regulation of expression of virulence factors and the exact timing of their expression is very important for many of the pathogenic bacteria, as most of them have to encounter different growth situations during an infection cycle, which require a fast adaptation to the new situation by the expression of different factors. This review gives an overview about the mechanisms used by pathogenic bacteria to accomplish the difficult task of regulation of their virulence potential in response to environmental changes. In addition, the relationship of these virulence regulatory systems with other signal transduction mechanisms not involved in pathogenicity is discussed.     

Signal transduction pathways of plant mitochondria: Retrograde regulation

Characteristic features and functional role of mitochondrial retrograde regulation (MRR) are considered. It is emphasized that MRR is manifested at mitochondria dysfunctions induced by mutations, chemical agents, or stresses and poorly studied so far. The data concerning gene expression of alternative oxidase involved in the restoration of mitochondrial functions are presented. The phenomenon of cytoplasmic male sterility controlled by MRR and also MRR involvement in plant cell responses to biotic and abiotic stresses (pathogen attack; oxygen, heat, and oxidative stresses) are described. Identified and putative components of MRR signaling pathways are discussed. Unique properties of the plant mitochondrial genome are described.     

Signal transduction mechanisms in the regulation of protein synthesis

Control of polypeptide synthesis plays an important role in cell proliferation and translation rates generally reflect the growth state of the cultured eukaryotic cell. Physiological regulation of protein synthesis is almost always exerted at the level of polypeptide chain initiation, with the binding of mRNA to the small ribosomal subunit a rate-limiting step in many cell systems. Studies have indicated key roles in the regulation of protein synthesis for the structural features of mRNA molecules and phosphorylation of initiation factors which catalyse this process. This review focusses on translational regulation at the level of mRNA binding to the ribosome and the role of phosphorylation of initiation factors in mediating both quantitative and qualitative control. The identity of putative kinases which may mediate these processes is addressed and a possible model for the role of a transient activation of initiation factors in cell growth or differentiation is presented.     

平滑肌收缩调节的信号转导

平滑肌细胞内信号转导主要有肌球蛋白轻链激酶（ＭＬＣＫ）和蛋白激酶Ｃ（ＰＫＣ）途径。前者通过肌浆内Ｃａ＾２＋浓度升高,激活钙调蛋白（ＣａＭ）依赖性ＭＬＣＫ,催化肌球蛋白轻链丝氨酸（Ｓｅｒ）－１９磷酸化,肌球蛋白ＡＴＰ酶活性增加,肌丝滑行,肌肉收缩。肌浆内Ｃａ＾２＋浓度的恢复使ＭＬＣＫ失活,肌球蛋白轻链磷酸酶（ＭＬＣＰ）使肌球蛋白脱磷酸化,肌肉舒张。近来有证据表明ＰＫＣ信号转导途径通过影响细肌丝相关蛋     

Signal transduction and the regulation of apoptosis: roles of ceramide

Knowledge about the molecular regulators of apoptosis is rapidly expanding. Cell death signals emanating from death receptors or internal cell injury detectors launch a number of signaling pathways which converge on several key families of proteins including specialized proteases and endonucleases which play a critical role in the execution of the death order. In this review, we summarize recent discoveries relating to the signaling pathways involved, the death receptors, the caspase family of apoptotic proteases, Bcl-2 family members, the sphingolipid ceramide, and the tumor suppressor p53. In particular, we focus on the role played by ceramide as a coordinator of the stress response and as a candidate biostat in the detection of cell injury.     

Signal transduction by VEGF receptors in regulation of angiogenesis and lymphangiogenesis

The VEGF/VPF (vascular endothelial growth factor/vascular permeability factor) ligands and receptors are crucial regulators of vasculogenesis, angiogenesis, lymphangiogenesis and vascular permeability in vertebrates. VEGF-A, the prototype VEGF ligand, binds and activates two tyrosine kinase receptors: VEGFR1 (Flt-1) and VEGFR2 (KDR/Flk-1). VEGFR1, which occurs in transmembrane and soluble forms, negatively regulates vasculogenesis and angiogenesis during early embryogenesis, but it also acts as a positive regulator of angiogenesis and inflammatory responses, playing a role in several human diseases such as rheumatoid arthritis and cancer. The soluble VEGFR1 is overexpressed in placenta in preeclampsia patients. VEGFR2 has critical functions in physiological and pathological angiogenesis through distinct signal transduction pathways regulating proliferation and migration of endothelial cells. VEGFR3, a receptor for the lymphatic growth factors VEGF-C and VEGF-D, but not for VEGF-A, regulates vascular and lymphatic endothelial cell function during embryogenesis. Loss-of-function variants of VEGFR3 have been identified in lymphedema. Formation of tumor lymphatics may be stimulated by tumor-produced VEGF-C, allowing increased spread of tumor metastases through the lymphatics. Mapping the signaling system of these important receptors may provide the knowledge necessary to suppress specific signaling pathways in major human diseases.     

Signal transduction in photoreceptors.

The biochemical role of the visual-pigment protein, rhodopsin, is reviewed, with reference to vertebrate rods and cones and the microvillar photoreceptors of invertebrates. New results are presented on the structure of squid rhodopsin, which possesses an extensive proline-rich repeat at its C-terminus, using negative-stain electron microscopy.     

Signal transduction in erythropoiesis.

The polypeptide hormone erythropoietin (Ep) is a growth factor whose actions on the erythroid progenitor cell induce proliferation and differentiation. The signal transduction system activated by Ep to mediate these cellular processes remains largely uncharacterized despite many years of research devoted to its elucidation. It is clear that an Ep receptor-mediated activation of adenylate cyclase or guanylate cyclase does not occur, although cAMP and cGMP may play modulatory roles. The role of calcium in the action of Ep is less clear. Although the presence of extracellular calcium seems to be an absolute requirement for Ep-induced proliferation, the positive changes induced by Ep in intracellular calcium occur with a time course suggestive of influx through ion channels opening within the cell membrane rather than release of intracellular stores by inositol trisphosphate. There is good evidence for the involvement of phospholipases A2 and C in the actions of Ep, including an early rise in lipoxygenase metabolites of arachidonic acid. Activation of phospholipase C can also result in the activation of protein kinase C in response to Ep. We present a model for the signal transduction pathway of Ep that is consistent with current knowledge and provides a framework for the coordinate actions of several intracellular mechanisms in the mediation of Ep-induced proliferation.