A recent report (Wu, H., Klingmuller, U., Besmer, P., and Lodish, H. F. (1995) Nature 377, 242-246) documents the interaction of the erythropoietin (EPO) receptor (EPOR) with the stem cell factor (SCF) receptor (c-KIT) and suggests that SCF acts through the EPOR. To elucidate the ability of SCF to affect the erythropoietin signaling pathway, we studied the effect of SCF on EPOR phosphorylation, SHC/ERK-1 activity, and cell proliferation and apoptosis in EPO-dependent HCD57 cells. Treatment of these cells with SCF resulted in phosphorylation of the EPOR. However, SCF-dependent phosphorylation of the EPOR did not initiate an EPO-like intracellular signal. SCF induced proliferation, SHC phosphorylation, and activation of ERK-1 but did not activate the JAK/STAT pathway. SCF stimulated SHC phosphorylation and ERK-1 activation independent of the EPOR in cells where the EPOR was down-regulated; the presence of the EPOR appeared to facilitate SCF activation of SHC and ERK-1. Furthermore, treatment of HCD57 cells with SCF increased cell number over a 3-day treatment, but apoptosis was observed in these cells. These data may illustrate two distinct pathways for erythroid cell proliferation and prevention of apoptosis in response to EPO, thereby providing a system to discriminate these intracellular signals. Erythropoietin (EPO)1 is the glycoprotein necessary for the proliferation, cell survival, and differentiation of immature erythroid cells (1). EPO acts on erythroid cells by binding the EPO receptor (EPOR), a member of the cytokine receptor superfamily (1). Although the EPOR contains no intrinsic tyrosine kinase activity, ligand binding to the receptor results in the rapid activation of the Janus kinase JAK2 and phosphorylation of the EPOR (2, 3). STAT5 binds to the activated receptor, becomes phosphorylated, and translocates to the nucleus where it binds DNA (4). Colony-forming units-erythroid and proerythroblasts are absolutely dependent on EPO for their survival; withdrawal of these cells from EPO results in apoptosis or programmed cell death (5, 6). The mechanism by which erythroid cells survive apoptosis is currently under investigation; JAK2 has been implicated in this pathway (7). However, the ability of EPO-dependent cell lines to survive without EPO through signaling via other cytokines has currently come under debate. A physical interaction between the receptor for EPO and the receptor for stem cell factor (SCF) was recently demonstrated in HCD57 cells (8). Wu and co-workers (8) in Dr. Harvey Lodish's laboratory also showed that SCF induced proliferation and phosphorylation of the EPOR in these EPO-dependent cells. This erythroleukemia cell line is a model for erythropoietin-dependent proliferation and erythroid cell survival (9, 10). We tested the possibility that SCF might be able to replace the cell survival and proliferative properties of EPO in this cell line. Our results confirmed the phosphorylation of the EPOR in HCD57 cells treated with SCF but could not confirm a role for SCF in erythroid cell survi...
Animal transgenic technology is one of the fastest growing biotechnology in the 21st century. It is used to integrate foreign genes into the animal genome by genetic engineering technology so that foreign genes can be expressed and inherited to the offspring. The transgenic efficiency and precise control of gene expression are the key limiting factors on preparation of transgenic animals. A variety of transgenic techniques are available, each of which has its own advantages and disadvantages and still needs further study because of unresolved technical and safety issues. With the in-depth research, the transgenic technology will have broad application prospects in the fields of exploration of gene function, animal genetic improvement, bioreactor, animal disease models, organ transplantation and so on. This article reviews the recently developed animal gene transfer techniques, including germline stem cell mediated method to improve the efficiency, gene targeting to improve the accuracy, RNA interference (RNAi)-mediated gene silencing technology, and the induced pluripotent stem cells (iPS) transgenic technology. The new transgenic techniques can provide a better platform for the study of trans-genic animals and promote the development of medical sciences, livestock production, and other fields.
High-mobility group box 2 (HMGB2) belongs to the HMG-box family that participates in a variety of biologic processes. Recent studies have suggested that HMGB2 plays an important role in the innate immunity of fish. Cherry Valley duck is the main duck bred for meat consumption in China, but there is limited research available on the impact of duck HMGB2 (duHMGB2) in antiviral innate immunity. Here, duHMGB2 genes were first cloned and analyzed from the spleen of Cherry Valley ducks. We show that duHMGB2 is widely distributed in most tissues of healthy ducks, and duHMGB2 was differentially expressed in three organs (the spleen, brain, and lung) of ducks during different viral infections. duHMGB2 is mainly expressed in the nucleus of duck embryo fibroblast (DEF) cells. However, duHMGB2 is released into the cytoplasm after viral infection. DuHMGB2 induced expression of several genes that regulate the immune response. Moreover, duHMGB2 activated and upregulatede transcription factor NF-κB promoter activity. We also used single gene manipulations (knockout or overexpression) to confirm that duHMGB2 can inhibit the replication of duck plague virus, duck Tembusu virus, and the novel duck reovirus in DEF cells. These data show that duHMGB2 can activate the antiviral innate immunity of the host. Thus, duHMGB2 may be considered an immune adjuvant against infectious diseases in duck.
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