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101.
1 Results Selective inhibition of protein tyrosine kinases is gaining importance as an effective therapeutic approach for the treatment of a wide range of human cancers.The epidermal growth factor receptor (EGFR) protein tyrosine kinase is one of the important kinases that play a fundamental role in cell growth signal pathways.We focused on the 4-anilinoquinazoline framework,which is observed in both compounds as a common structure.A boron atom has a vacant orbital and interconverts with ease between th... 相似文献
102.
Spindle checkpoint is an important biochemical signaling cascade during mitosis which monitors the fidelity of chromosome
segregation, and is mediated by protein kinases Mps1 and Bub1/BubR1. Our recent studies show that kinesin-related motor protein
CENP-E interacts with BubR1 and participates in spindle checkpoint signaling. To elucidate the molecular mechanisms underlying
spindle checkpoint signaling, we carried out proteomic dissection of human cell kinetochore and revealed protein kinase TTK,
human homologue of yeast Mps1. Our studies show that TTK is localized to the kinetochore of human cells, and interacts with
CENP-E, suggesting that TTK may play an important role in chromosome segregation during mitosis. 相似文献
103.
Krempler A Kartarius S Günther J Montenarh M 《Cellular and molecular life sciences : CMLS》2005,62(12):1379-1387
104.
Ethanol-induced cerebellar hypoplasia is associated with inhibition of insulin-stimulated survival signaling. The present work explores the mechanisms of impaired insulin signaling in a rat model of fetal alcohol syndrome. Real-time quantitative RT-PCR demonstrated reduced expression of the insulin gene in cerebella of ethanol-exposed pups. Although receptor expression was unaffected, insulin and insulin-like growth factor (IGF-I) receptor tyrosine kinase (RTK) activities were reduced by ethanol exposure, and these abnormalities were associated with increased PTP1b activity. In addition, glucose transporter molecule expression and steady-state levels of ATP were reduced in ethanol-exposed cerebellar tissue. Cultured cerebellar granule neurons from ethanol-exposed pups had reduced expression of genes encoding insulin, IGF-II, and the IGF-I and IGF-II receptors, and impaired insulin- and IGF-I-stimulated glucose uptake and ATP production. The results demonstrate that ethanol inhibits insulin-mediated actions in the developing brain by reducing local insulin production and insulin RTK activation, leading to inhibition of glucose transport and ATP production.Received 30 December 2004; received after revision 1 March 2005; accepted 10 March 2005 相似文献
105.
Marchetta M Gamberi T Sarno S Magherini F Raugei G Camici G Pinna LA Modesti A 《Cellular and molecular life sciences : CMLS》2004,61(10):1176-1184
Although the yeast genome does not encode bona fide protein tyrosine kinases, tyrosine-phosphorylated proteins are numerous, suggesting that besides dual-specificity kinases, some Ser/Thr kinases are also committed to tyrosine phosphorylation in Saccharomyces cerevisiae. Here we show that blockage of the highly pleiotropic Ser/Thr kinase CK2 with a specific inhibitor synergizes with the overexpression of Stp1 low-molecular-weight protein tyrosine phosphatase (PTP) in inducing a severe growth-defective phenotype, consistent with a prominent role for CK2 in tyrosine phosphorylation in yeast. We also present in vivo evidence that immunophilin Fpr3, the only tyrosine-phosphorylated CK2 substrate recognized so far, interacts with and is dephosphorylated by Spt1. These data disclose a functional correlation between CK2 and LMW-PTPs, and suggest that reversible phosphorylation of Fpr3 plays a role in the regulation of growth rate and budding in S. cerevisiae.Received 15 January 2004; received after revision 20 February 2004; accepted 4 March 2004 相似文献
106.
Guthmann F Maehl P Preiss J Kolleck I Rüstow B 《Cellular and molecular life sciences : CMLS》2002,59(11):1999-2003
Glycoprotein IV (FAT/CD36) has been shown to be phosphorylated by a cAMP-dependent, platelet membrane-bound ectokinase. In
this study, we demonstrate that ectophosphorylation of FAT/CD36 regulates initial palmitate uptake. This is the first time
that short-term regulation of the activity of a long-chain fatty acid carrier could be shown. Phosphorylation of FAT/CD36
was paralleled by a significant decrease in initial palmitate uptake by morphologically and functionally intact platelets.
Maximum inhibition of palmitate uptake was achieved at 0.5 nM extracellular ATP, being significantly decreased to 72% compared
to the control. Inhibition of palmitate uptake was abolished by co-incubation with the specific protein kinase A inhibitor
peptide PKI or with β,γ-methylene-ATP, and was reversible upon addition of alkaline phosphatase. An extracellular ATP concentration
above 5 μM completely prevented the ectophosphorylation-mediated inhibition of palmitate uptake. We conclude that FAT/CD36-mediated
palmitate uptake by human platelets is short-term regulated via cAMP-dependent ectophosphorylation of FAT/CD36.
Received 18 July 2002; received after revision 29 August 2002; accepted 19 September 2002
RID="*"
ID="*"Corresponding author. 相似文献
107.
108.
The intracellular signaling pathways mediating the nuclear exclusion of the androgen receptor (AR) by melatonin were evaluated
in PC3 cells stably transfected with the AR. The melatonin-induced nuclear exclusion of the AR by melatonin (100 nM, 3 h)
was blocked by LY 83583 (an inhibitor of guanylyl cyclases). 8-Bromo-cGMP (a cell-permeable cGMP analog), mimicked the effect
of melatonin, as did ionomycin (a calcium ionophore) and PMA [an activator of protein kinase C (PKC)], and their effects were
blocked by GF-109203X (a selective PKC inhibitor). BAPTA (an intracellular calcium chelator) blocked the effects of melatonin
and 8-bromo-cGMP but not of PMA. Inhibition or activation of the protein kinase A pathway did not affect basal or melatonin-mediated
AR localization. We conclude that the melatonin-mediated rise in cGMP elicits AR nuclear exclusion via a pathway involving
increased intracellular calcium and PKC activation. These results define a novel signaling pathway that regulates AR localization
and androgen responses in target cells.
Received 31 July 2001; received after revision 18 September 2001; accepted 30 October 2001 相似文献
109.
Mechanisms of self-incompatibility in flowering plants 总被引:14,自引:0,他引:14
Self-incompatibility is a widespread mechanism in flowering plants that prevents inbreeding and promotes outcrossing. The
self-incompatibility response is genetically controlled by one or more multi-allelic loci, and relies on a series of complex
cellular interactions between the self-incompatible pollen and pistil. Although self-incompatibility functions ultimately
to prevent self-fertilization, flowering plants have evolved several unique mechanisms for rejecting the self-incompatible
pollen. The self-incompatibility system in the Solanaceae makes use of a multi-allelic RNase in the pistil to block incompatible pollen tube growth. In contrast, the Papaveraceae system appears to have complex cellular responses such as calcium fluxes, actin rearrangements, and programmed cell death
occurring in the incompatible pollen tube. Finally, the Brassicaceae system has a receptor kinase signalling pathway activated in the pistil leading to pollen rejection. This review highlights
the recent advances made towards understanding the cellular mechanisms involved in these self-incompatibility systems and
discusses the striking differences between these systems.
Received 10 May 2001; received after revision 20 June 2001; accepted 20 June 2001 相似文献
110.
Fig. The absorption 《科学通报(英文版)》2000,45(10):914-920
Histidine coordinated to Chi a is a distinct characteristic of Chl ain vivo. By using histidine analogue of 1-methylimidazole (C4H6N22) and measuring the UV/vis absorption, CD and MCD spectra of the interaction between C4H6N2 and Chl a in CCI4, we have obtained that: (i) In pure CCl4 solvent, Chl a molecule is in five-coordinate state, and two Chl a molecules form an asymmetric compact-dimer with strong
coupling interaction. We propose that the two Chl a molecules are connected by two unequally coordinated Mg-O bonds (the two
oxygen atoms come from the C=O of C131 keto and C17 ester, respectively); (ii) when the molar ratio of C4H6N2/Chl a is 0.5 or 1 (corresponding to 2Chl a · 1C4H6N2 and 2Chl a · 2C4H6N2, respectively), significant changes have been observed in the absorption, CD and MCD spectra, which indicate that the Chl
a remains in dimer form, but the coupling interaction between them reduces greatly. We postulate that C4H6N2 replaces the ligation of C=O of C17 ester and C131 keto to Mg atoms sequentially. The two Chl a molecules linked by two weakly interacted Mg…O bonds form a relaxed-dimer. The
structure of the model is essentially similar to that of the primary electronic donor, P680, of photosystem II in high plants and algae. 相似文献