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131.
Tyrosine Phosphorylation of A17 during Vaccinia Virus Infection: Involvement of the H1 Phosphatase and the F10 Kinase 下载免费PDF全文
Vaccinia virus encodes two protein kinases (B1 and F10) and a dual-specificity phosphatase (VH1), suggesting that phosphorylation and dephosphorylation of substrates on serine/threonine and tyrosine residues are important in regulating diverse aspects of the viral life cycle. Using a recombinant in which expression of the H1 phosphatase can be regulated experimentally (vindH1), we have previously demonstrated that repression of H1 leads to the maturation of noninfectious virions that contain several hyperphosphorylated substrates (K. Liu et al., J. Virol. 69:7823-7834). In this report, we demonstrate that among these is a 25-kDa protein that is phosphorylated on tyrosine residues in H1-deficient virions and can be dephosphorylated by recombinant H1. We demonstrate that the 25-kDa phosphoprotein represents the product of the A17 gene and that A17 is phosphorylated on serine, threonine, and tyrosine residues during infection. Detection of phosphotyrosine within A17 is abrogated when Tyr(203) (but not Tyr(3), Tyr(6), or Tyr(7)) is mutated to phenylalanine, suggesting strongly that this amino acid is the site of tyrosine phosphorylation. Phosphorylation of A17 fails to occur during nonpermissive infections performed with temperature-sensitive mutants defective in the F10 kinase. Our data suggest that this enzyme, which was initially characterized as a serine/threonine kinase, might in fact have dual specificity. This hypothesis is strengthened by the observation that Escherichia coli induced to express F10 contain multiple proteins which are recognized by antiphosphotyrosine antiserum. This study presents the first evidence for phosphotyrosine signaling during vaccinia virus infection and implicates the F10 kinase and the H1 phosphatase as the dual-specificity enzymes that direct this cycle of reversible phosphorylation. 相似文献
132.
133.
The orchestrated movement of cells of the immune system is essential to generation of productive responses leading to protective memory development. Recent advances have allowed the direct microscopic visualization of lymphocyte and antigen-presenting cell migration and interaction during immune response initiation and progression. These studies have defined important characteristics of the microanatomy of lymphocyte movement, particularly in the lymph node. Moreover, the ability to track endogenous antigen-specific T cells has revealed a coordinated pathway of CD8 T cell movement in the spleen following primary and secondary infection. As a consequence, the local anatomy of secondary lymphoid tissues during infection has emerged as a critical regulator of immunity. While some of the factors responsible for the migratory cues instructing immune cell movement have been identified, much remains to be learned. Here, we provide a brief overview of studies examining CD8 T cell localization during the immune response to infection in the context of our current understanding of immune system structure. 相似文献
134.
Vascularization, under physiological or pathophysiological conditions, typically takes place by one or more of the following processes: angiogenesis, vasculogenesis, arteriogenesis, and lymphangiogenesis. Although all of these mechanisms of vascularization have sufficient contrasting features to warrant consideration under separate cover, one common feature shared by all is their sensitivity to the VEGF signaling pathway. Conditions such as wound healing and physical exercise result in increased production of reactive oxygen species such as H(2)O(2), and both are associated with increased tissue vascularization. Understanding these two scenarios of adult tissue vascularization in tandem offers the potential to unlock the significance of redox regulation of the VEGF signaling pathway. Does H(2)O(2) support tissue vascularization? H(2)O(2) induces the expression of the most angiogenic form of VEGF, VEGF-A, by a HIF-independent and Sp1-dependent mechanism. Ligation of VEGF-A to VEGFR2 results in signal transduction leading to tissue vascularization. Such ligation generates H(2)O(2) via an NADPH oxidase-dependent mechanism. Disruption of VEGF-VEGFR2 ligation-dependent H(2)O(2) production or decomposition of such H(2)O(2) stalls VEGFR2 signaling. Numerous antioxidants exhibit antiangiogenic properties. Current evidence lends firm credence to the hypothesis that low-level endogenous H(2)O(2) supports vascular growth. 相似文献
135.
Involvement of Exo1b in DNA damage-induced apoptosis 总被引:1,自引:0,他引:1
Emma Bolderson Derek J. Richard Winfried Edelmann Kum Kum Khanna 《Nucleic acids research》2009,37(10):3452-3463
Apoptosis is essential for the maintenance of inherited genomic integrity. During DNA damage-induced apoptosis, mechanisms of cell survival, such as DNA repair are inactivated to allow cell death to proceed. Here, we describe a role for the mammalian DNA repair enzyme Exonuclease 1 (Exo1) in DNA damage-induced apoptosis. Depletion of Exo1 in human fibroblasts, or mouse embryonic fibroblasts led to a delay in DNA damage-induced apoptosis. Furthermore, we show that Exo1 acts upstream of caspase-3, DNA fragmentation and cytochrome c release. In addition, induction of apoptosis with DNA-damaging agents led to cleavage of both isoforms of Exo1. The cleavage of Exo1 was mapped to Asp514, and shown to be mediated by caspase-3. Expression of a caspase-3 cleavage site mutant form of Exo1, Asp514Ala, prevented formation of the previously observed fragment without any affect on the onset of apoptosis. We conclude that Exo1 has a role in the timely induction of apoptosis and that it is subsequently cleaved and degraded during apoptosis, potentially inhibiting DNA damage repair. 相似文献
136.
Maroof Husain Rakesh Shukla Madhu Dikshit Pradeep K. Maheshwari Devika Nag Rikhab C. Srimal Prahlad K. Seth Vinay K. Khanna 《Neurochemical research》2009,34(8):1427-1432
A case-control study was undertaken to investigate the status of platelet monoamine oxidase-B (MAO-B) activity in Indian cases
of idiopathic Parkinson’s disease. A significant increase in the activity of platelet MAO-B was observed in Parkinson’s cases
(n = 26) as compared to controls (n = 26). No significant change in the activity of the enzyme was observed while the data was analysed with respect to age,
sex and duration of disease. A trend of decrease in platelet MAO-B activity was observed in Parkinson’s cases with respect
to stage although the change was not significant. No correlation in platelet MAO-B activity was observed with respect to age
and sex in the control subjects. Parkinson’s cases treated with L-DOPA and MAO-B inhibitor exhibited decreased platelet MAO-B
activity as compared to drug naive cases and those treated with L-DOPA alone. Interestingly, Parkinson’s cases treated with
L-DOPA and amantadine also had lower platelet MAO-B activity as compared to drug naive cases and those treated with L-DOPA
alone. Activity of platelet MAO-B in Parkinson’s patients was increased in naive cases and those treated with L-DOPA alone
or in combination with other drugs compared to controls. The results of the present study indicate that phenotypic activity
of platelet MAO-B is high in Indian Parkinson’s cases. Further, action mechanism of drugs used in the treatment of Parkinson’s
disease could be understood by assay of platelet MAO-B activity. It is an interesting observation and may be looked further
in large number of cases. 相似文献
137.
Samir Ghosh Anup Kumar Misra Gitika Bhatia M.M. Khan A.K. Khanna 《Bioorganic & medicinal chemistry letters》2009,19(2):386-389
A series of N-per-O-acetyl-glucosyl arylthiosemicarbazide and thiosemicarbazone derivatives have been synthesized and evaluated for their in vivo anti-dyslipidemic and in vitro antioxidant activities. Among 16 compounds tested, 3 compounds showed potent anti-dyslipidemic activity and 6 compounds showed potent antioxidant and scavenger of oxygen free radicals activity. 相似文献
138.
Bella Devassy Tony Dinesh Goyal Sunil Khanna 《International biodeterioration & biodegradation》2009,63(4):462-469
The decolorization potential of two bacterial consortia developed from a textile wastewater treatment plant showed that among the two mixed bacterial culture SKB-II was the most efficient in decolorizing individual as well as mixture of dyes. At 1.3 g L?1 starch supplementation in the basal medium by the end of 120 h decolorization of 80–96% of four out of the six individual azo dyes Congo red, Bordeaux, Ranocid Fast Blue and Blue BCC (10 mg L?1) was noted. The culture exhibited good potential ability in decolorizing 50–60% of all the dyes (Congo red, Bordeaux, Ranocid Fast Blue and Blue BCC) when present as a mixture at 10 mg L?1. The consortium SKB-II consisted of five different bacterial types identified by 16S rDNA sequence alignment as Bacillus vallismortis, Bacillus pumilus, Bacillus cereus, Bacillus subtilis and Bacillus megaterium which were further tested to decolorize dyes. The efficient ability of this developed consortium SKB-II to decolorize individual dyes and textile effluent using packed bed reactors is being carried out. 相似文献
139.
Dysfunction of primary cilia due to mutations in cilia-centrosomal proteins is associated with pleiotropic disorders. The
primary (or sensory) cilium of photoreceptors mediates polarized trafficking of proteins for efficient phototransduction.
Retinitis pigmentosa GTPase regulator (RPGR) is a cilia-centrosomal protein mutated in >70% of X-linked RP cases and 10%–20%
of simplex RP males. Accumulating evidence indicates that RPGR may facilitate the orchestration of multiple ciliary protein
complexes. Disruption of these complexes due to mutations in component proteins is an underlying cause of associated photoreceptor
degeneration. Here, we highlight the recent developments in understanding the mechanism of cilia-dependent photoreceptor degeneration
due to mutations in RPGR and RPGR-interacting proteins in severe genetic diseases, including retinitis pigmentosa, Leber congenital
amaurosis (LCA), Joubert syndrome, and Senior-Loken syndrome, and explore the physiological relevance of photoreceptor ciliary
protein complexes. 相似文献
140.