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81.
Src kinase activity was found to protect endothelial cells from apoptosis during vascular endothelial growth factor (VEGF)-, but not basic fibroblast growth factor (bFGF)-, mediated angiogenesis in chick embryos and mice. In fact, retroviral targeting of kinase-deleted Src to tumor-associated blood vessels suppressed angiogenesis and the growth of a VEGF-producing tumor. Although mice lacking individual Src family kinases (SFKs) showed normal angiogenesis, mice deficient in pp60c-src or pp62c-yes showed no VEGF-induced vascular permeability (VP), yet fyn-/- mice displayed normal VP. In contrast, inflammation-mediated VP appeared normal in Src-deficient mice. Therefore, VEGF-, but not bFGF-, mediated angiogenesis requires SFK activity in general, whereas the VP activity of VEGF specifically depends on the SFKs, Src, or Yes. 相似文献
82.
A new XRCC1-containing complex and its role in cellular survival of methyl methanesulfonate treatment 总被引:10,自引:0,他引:10 下载免费PDF全文
Luo H Chan DW Yang T Rodriguez M Chen BP Leng M Mu JJ Chen D Songyang Z Wang Y Qin J 《Molecular and cellular biology》2004,24(19):8356-8365
DNA single-strand break repair (SSBR) is important for maintaining genome stability and homeostasis. The current SSBR model derived from an in vitro-reconstituted reaction suggests that the SSBR complex mediated by X-ray repair cross-complementing protein 1 (XRCC1) is assembled sequentially at the site of damage. In this study, we provide biochemical data to demonstrate that two preformed XRCC1 protein complexes exist in cycling HeLa cells. One complex contains known enzymes that are important for SSBR, including DNA ligase 3 (DNL3), polynucleotide kinase 3'-phosphatase, and polymerase beta; the other is a new complex that contains DNL3 and the ataxia with oculomotor apraxia type 1 (AOA) gene product aprataxin. We report the characterization of the new XRCC1 complex. XRCC1 is phosphorylated in vivo and in vitro by CK2, and CK2 phosphorylation of XRCC1 on S518, T519, and T523 largely determines aprataxin binding to XRCC1 though its FHA domain. An acute loss of aprataxin by small interfering RNA renders HeLa cells sensitive to methyl methanesulfonate treatment by a mechanism of shortened half-life of XRCC1. Thus, aprataxin plays a role to maintain the steady-state protein level of XRCC1. Collectively, these data provide insights into the SSBR molecular machinery in the cell and point to the involvement of aprataxin in SSBR, thus linking SSBR to the neurological disease AOA. 相似文献
83.
At the University of Pittsburgh School of Medicine, our experience with urethrolysis over the past several years offered a unique opportunity to assess outcomes after delayed time to urethrolysis. We observed a highly suggestive association between prolonged time to urethrolysis and a greater likelihood of persistent bladder dysfunction. If this observation is corroborated by other studies, it would be prudent to lower our threshold of clinical suspicion to detect bladder outlet obstruction. Videourodynamics testing can be invaluable for making the distinction between outlet obstruction versus de novo urge incontinence. Here, we briefly review the literature on urethrolysis and present the urethrolysis technique utilized at our institution. The article concludes with several challenging and controversial clinical judgment questions asked ofDr Leng by Dr Chancellor. 相似文献
84.
The SARS-associated coronavirus (SARS-CoV) main proteinase is a key enzyme in viral polyprotein processing. To allow structure-based design of drugs directed at SARS-CoV main proteinase, we predicted its binding pockets and affinities with existing HIV, psychotic and parasite drugs (lopinavir, ritonavir, niclosamide and promazine), which show signs of inhibiting the replication of SARS-CoV. Our results suggest that these drugs and another two HIV inhibitors (PNU and UC2) could be used as templates for designing SARS-CoV proteinase inhibitors. 相似文献
85.
Lingling?Wang Li?Ma Wenchuan?Leng Jian?Yang Junping?Zhu Jie?Dong Ying?Xue Zhe?Wan Ruoyu?Li Qi?JinEmail author 《中国科学C辑(英文版)》2004,47(5):389-395
Trichophyton rubrum (T. rubrum) is the most common of the superficial fungi. In an effort to better understand the genetic and biochemical makeup ofT. rubrum, we generated cDNA libraries from 3 growth stages and used these to isolate 4002 unique expressed sequence tags (ESTs). Sequence
comparisons with the Genbank database allowed 1226 of the ESTs to be assigned putative functions or matched with homologs
from other organisms. Of the remaining ESTs, 989 were only weakly similar to known sequences and 1787 had no identifiable
functions, suggesting that they represent novel genes. We further analyzed the presence of several important genes involved
in the growth, metabolism, signal transduction, pathogenesis and drug resistance inT. rubrum. This information was used to newly elucidate important metabolic pathways inT. rubrum. Taken together, our results should form the molecular basis for continued research on the physiological processes and pathogenic
mechanisms ofT. rubrum, and may lead to a better understanding of fungal drug resistance and identification of new drug targets. 相似文献
86.
BPGAP1 interacts with cortactin and facilitates its translocation to cell periphery for enhanced cell migration 下载免费PDF全文
Rho GTPases control cell dynamics during growth and development. They are activated by guanine nucleotide exchange factors and inactivated by GTPase-activating proteins (GAPs). Many GAPs exist with various protein modules, the functions of which largely remain unknown. We recently cloned and identified BPGAP1 as a novel RhoGAP that coordinately regulates pseudopodia and cell migration via the interplay of its BNIP-2 and Cdc42GAP homology, RhoGAP, and the proline-rich domains. To further elucidate the molecular mechanism underlying cell dynamics control by BPGAP1, we used protein precipitations and matrix-assisted laser desorption/ionization mass spectrometry and identified cortactin, a cortical actin binding protein as a novel partner of BPGAP1 both in vitro and in vivo. Progressive deletion studies confirmed that cortactin interacted directly and constitutively with the proline-rich motif 182-PPPRPPLP-189 of BPGAP1 via its Src homology 3 domain. Together, they colocalized to periphery and enhanced cell migration. Furthermore, substitution of prolines at 184 and 186 with alanines abolished their interaction. Consequently, this BPGAP1 mutant failed to facilitate translocation of cortactin to the periphery, and no enhanced cell migration was observed. These results provide the first evidence that a RhoGAP functionally interacts with cortactin and represents a novel determinant in the regulation of cell dynamics. 相似文献
87.
Four species of Adlerius phlebotomine sandflies have been recorded in China, namely: P. chinensis Newstead, 1916 (Pc), P. fengi Leng & Zhang, 1994; P. longiductus Parrot, 1928 and P. sichuanensis Leng & Yin, 1983 (Ps). Adlerius phlebotomies are the main vectors of visceral leishmaniasis (VL) in China; three of them are acknowledged as VL vectors and P. fengi is considered a potential VL vector for southwestern mountainous region. Different opinion has been raised to the validity of identity of Ps by some investigators from Shanghai and Shanxi who consider Ps to be a large type of Pc instead of an isolate species. The center of controversy is whether Ps is an isolate taxon or a large type of Pc. The present authors have carried out a series of comparative studies for these two flies on: 1 quantitative and qualitative morphological characters of four Chinese Adlerius phlebotomies; and 2. differences in geographical distribution. All specimens of Pc and Ps used in the present study are collected where their holotypes-paratypes were produced--West Mountain, West Suburb, Beijing and Lixian County, Sichuan Province. The results have forcefully proved that Ps is an isolate species instead of a so-called large type Pc according to the concept of species. The clarification of their taxonomical identities is meaningful because both of them are VL vectors in different epidemic areas in China; especially Ps is an important VL vector in high mountainous regions of southwestern China and some extend to the Loess Plateau of northwestern China, where VL still exists and it is also the first Phlebotomine sandfly discovered in Tibet, the locality being near Assam in India (Leng et al. 1990). 相似文献
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Chronic immune activation is associated with impaired signal transduction. Since such activation is commonly found during HIV-1 infection, we studied cellular responses to non-specific T-cell receptor stimulation of PBMC obtained from 20 HIV-1 non-infected individuals and 23 highly or partially immune activated HIV-1 infected individuals. PBMC proliferation and ERK-1/2 phosphorylation following anti-CD3 stimulation, and constitutive levels of Cbl-b, were determined. Increased levels of Cbl-b, decreased proliferation, and lower ERK-1/2 phosphorylation were found in PBMC of highly immune activated HIV-1 infected individuals. The elevated expression of Cbl-b and impaired phosphorylation of ERK-1/2 associated with immune activation probably contribute to the attenuated proliferative and cellular responses characteristic of HIV-1 infection. Therefore, targeting immune negative modulators, such as Cbl-b, may serve as a novel approach for controlling HIV-1 disease progression. 相似文献