Signal transduction through interferon-gamma receptor on human eosinophils

BACKGROUND: We reported on the constitutive interferon-gamma receptor (IFN-gammaR) expression on eosinophils. But signal transduction through IFN-gammaR on eosinophils remains to be elucidated. In this study, we examined the involvement of the Jak/Stat pathway in the signaling of eosinophils after IFN-gammaR conjugation by the ligand binding. METHODS: Purified peripheral eosinophils were stimulated with IFN-gamma at 37 degrees C for 1-60 min. Tyrosine phosphorylation of IFN-gammaR, Jak1, Jak2, and Stat1alpha was examined by immunoblotting. Gel-shift assay was also examined to show the formation of Stat1alpha-DNA complexes. RESULTS: We show that binding of IFN-gamma to human eosinophils initiated a series of events that resulted in the rapid tyrosine phosphorylation of not only the IFN-gammaRalpha chain but also Jak1, Jak2, and Stat1alpha. In addition, IFN-gamma enhanced the DNA-binding activity of Stat1alpha. CONCLUSION: These data indicate that IFN-gamma affects eosinophils through its specific receptor and utilizes the Jak/Stat pathway as its mode of signaling.     

衰老的信号转导

长生不老是每个人的最大心愿，这在以前只能是一个梦想，然而，在科学技术尤其是分子生物学技术高度发达的今天，这一梦想将可能变为现实，事实上研究人员通过分子生物学方法抑制衰老信号转导途径的衰老基因表达已经在细胞水平能够延缓细胞的衰老，从这里我们可以看出衰老信号转导研究对抗衰老研究至关重要，事实上衰老的信号转导研究已经成为衰老研究和抗衰老研究最有吸引力的领域之一，本文就这一领域的最新进展作一综述。     

Signal transduction targets in invasion

The processes of physiologic and malignant invasion use the same cellular pathways, albeit under differential regulation. Critical signaling messages can be initiated through cell-cell and cell-substratum contact, as well as using autocrine and paracrine activation. Cancer cells are known for their flexibility and autocrine functions, however, they still rely on a battery of important signaling events. The interaction between the tumor cell and the stroma provides an important signaling milieu and target zone for molecular therapeutic intervention. It is now recognized that malignant invasion requires that interaction for optimal signaling and function. New technologies are now available to allow more rapid dissection of these pathways and characterization of unique regulatory sites for therapeutic gain. This revised version was published online in July 2006 with corrections to the Cover Date.     

Signal transduction in B lymphocytes

We have examined the activity and intracellular compartmentalization of protein kinase C (PKC) following activation of human B lymphocytes by anti-human leukocyte antigen (HLA) class II antibodies. 12-O-Tetradecanoylphorbol 13-acetate (TPA) treatment increased membrane-associated PKC (between five and nine times greater than the control value) and decreased cytosolic PKC (between 70% and 100% of the control value). In contrast, anti-class II antibodies induce an activation of PKC which results either in an increase of cytosolic activity or membrane-bound activity without redistribution of cytosolic PKC. The effect of TPA and HLA class II molecules on total PKC activity was comparable: when TPA induced an increase of total PKC activity so did HLA class II molecules and when TPA did not, HLA class II molecules did not. Measurement on SDS PAGE of histone phosphorylation confirmed the above results of PKC activity. Taken together, our results suggest that PKC might be implicated in HLA class II-induced B lymphocyte activation.     

Signal transduction in T cells.

Rapid progress was made during the past year in the delineation of the nature of the initial biochemical events triggered by the T-cell antigen receptor. Antigen-mediated activation of phospholipase C was demonstrated to require protein tyrosine phosphorylation and, most surprising, activation of the Ras family of signal transduction molecules was shown to closely follow stimulation of the T-cell antigen receptor. Major controversy continues over which events are relevant to the various effector functions of T cells.     

上皮-间质转化的信号转导机制

上皮-间质转化(epithelial-mesenchymal transition,EMT)出现在各种生理和病理情况下,在胚胎发生与器官发育、肿瘤形成和转移以及纤维化过程中均有表现。TGF-β是EMT的一个重要诱导因素,其通过Smad和非Smad依赖通路对EMT的发生进行调节,对肿瘤的形成、转移和扩散起到了重要的作用。本文综述了近年来EMT信号转导机制的研究进展。     

Signal transduction during in vitro lymphocyte homing

Lymphocyte binding to endothelium is a necessary prerequisite for lymphocyte homing through endothelium. This is mediated by the binding of ligands on endothelial cells to lymphocyte surface homing receptors. We show in this paper that the intracellular second messenger pathways involved in interferon gamma-induced intercellular adhesion molecule 1 upregulation on endothelial cells are protein kinase C and calcium dependent. Lymphocyte binding to endothelial cells is enhanced by both platelet activating factor and interleukin 1 alpha. Platelet activating factor added to endothelial cultures increases lymphocyte binding within 10 min and operates via protein kinase C but not via cAMP. On the other hand interleukin 1 alpha increases binding within 4 hr and operates via cAMP but not via protein kinase C. These results imply that different mediators of inflammation can activate different signal transduction pathways but lead to similar increases in lymphocyte binding.     

Signal transduction during Fc receptor-mediated phagocytosis

Phagocytosis is the process whereby cells engulf large particles, usually over 0.5 micro m in diameter. Phagocytosis is triggered by the interaction of opsonins that cover the particle to be internalized with specific receptors on the surface of the phagocyte. The best-studied phagocytic receptors include the Fc receptors (FcR) that bind to the Fc portion of immunoglobulins. Cross-linking of FcR on the phagocyte initiates a variety of signals, which lead through the reorganization of the actin cytoskeleton, and membrane remodeling, to the formation of the phagosome. From recent data, it is becoming clear that FcR-mediated phagocytosis occurs as a series of steps that are regulated in a nonlinear manner and that signaling for phagocytosis does not terminate when the phagosome is formed. Several lipid molecules localize around the nascent phagosome and function as initiators of important signaling pathways for the late stages of phagolysosome formation. In addition, the use of particular signaling molecules may change for different receptors and may also vary depending on the activation or differentiation state of the cell. This review focuses on this new information and presents a model of our present understanding of the signal transduction events that regulate phagocytosis mediated by FcR.     

信号转导通路与食管癌

食管癌是我国最常见的恶性肿瘤之一,其明显的地域性分布是食管癌流行病学的突出特点,其中河南省等地区尤为高发。20世纪50年代末,我国科学家就开始深入河南林县,进行大规模的人群调查,发现该地区食管癌发病率之高是罕见的。在过去的几十年里,我国老一代科学家在这些地区进行了多学科、系统性的综合研究,通过流行病学调查、