The interaction between dansyl-labeled pollen calmodulin (D-pCaM) and synthesized peptides was studied in the presence of Ca2+ by fluorescence spectra. It is Found that Gly/L-Ala --> D-Ala substitution in peptide c...The interaction between dansyl-labeled pollen calmodulin (D-pCaM) and synthesized peptides was studied in the presence of Ca2+ by fluorescence spectra. It is Found that Gly/L-Ala --> D-Ala substitution in peptide chains caused great changes in their affinity for pCaM. Besides. our data provided evidence on the dissimilarity of different CaMs although they have highly-conserved structures. A preliminary study was carried out on the effects of CaM-binding peptides on cellular signal transduction, cell proliferation, showing the participation of CaM in cell functions mentioned above.展开更多
In cells, the interactions of distinct signaling transduction pathways originating from cross-talkings between signaling molecules give rise to the formation of signaling transduction networks, which contributes to th...In cells, the interactions of distinct signaling transduction pathways originating from cross-talkings between signaling molecules give rise to the formation of signaling transduction networks, which contributes to the changes (emergency) of kinetic behaviors of signaling system compared with single molecule or pathway. Depending on the known experimental data, we have constructed a model for complex cellular signaling transduction system, which is derived from signaling transduction of epidermal growth factor receptor in neuron. By the computational simulating methods, the self-adaptive controls of this system have been investigated. We find that this model exhibits a relatively stable selfadaptive system, especially to over-stimulation of agonist, and the amplitude and duration of signaling intermediates in it could be controlled by multiple self-adaptive effects, such as 'signal scattering', 'positive feedback', 'negative feedback' and 'B-Raf shunt'. Our results provide an approach to understanding the dynamic behaviors of complex biological systems.展开更多
Studies on cell signaling pay more attention to spatial dynamics and how such diverse organization can relate to high order of cellular capabilities.To overview the specificity of cell signaling,we integrated human re...Studies on cell signaling pay more attention to spatial dynamics and how such diverse organization can relate to high order of cellular capabilities.To overview the specificity of cell signaling,we integrated human receptome data with proteome spatial expression profiles to systematically investigate the specificity of receptors and receptor-triggered transduction networks across 62 normal cell types and 14 cancer types.Six percent receptors showed cell-type-specific expression,and 4% signaling networks presented enriched cell-specific proteins induced by the receptors.We introduced a concept of“response context”to annotate the cell-type dependent signaling networks.We found that most cells respond similarly to the same stimulus,as the“response contexts”presented high functional similarity.Despite this,the subtle spatial diversity can be observed from the difference in network architectures.The architecture of the signaling networks in nerve cells displayed less completeness than that in glandular cells,which indicated cellular-context dependent signaling patterns are elaborately spatially organized.Likewise,in cancer cells most signaling networks were generally dysfunctional and less complete than that in normal cells.However,glioma emerged hyper-activated transduction mechanism in malignant state.Receptor ATP6AP2 and TNFRSF21 induced rennin-angiotensin and apoptosis signaling were found likely to explain the glioma-specific mechanism.This work represents an effort to decipher context-specific signaling network from spatial dimension.Our results indicated that although a majority of cells engage general signaling response with subtle differences,the spatial dynamics of cell signaling can not only deepen our insights into different signaling mechanisms,but also help understand cell signaling in disease.展开更多
Cyclic ADP-ribose (cADPR) is a universal Ca2+ mobilizing second messenger in many different cell types and organisms. cADPR activates Ca2+ release from endo/sarcoplasmic reticulum via ryanodine receptors. In addition,...Cyclic ADP-ribose (cADPR) is a universal Ca2+ mobilizing second messenger in many different cell types and organisms. cADPR activates Ca2+ release from endo/sarcoplasmic reticulum via ryanodine receptors. In addition, Ca2+ entry secondary to Ca2+ depletion is at least one of the mechanisms in which cADPR triggers Ca2+ inflow, too. Analogues of cADPR have been prepared by chemical and chemo-enzymatic routes. Most of the analogues were analyzed for biological activity in intact or permeabilized Jurkat T cells (a human T-lymphoma cell line). As a systematic approach, analogues were grouped according to alterations in the base, the northern ribose, the southern ribose, the pyrophosphate backbone, or in complex modifications, comprising more than one part of the molecule. Biological activity of the analogues is reviewed, with special emphasis on Jurkat T cells.展开更多
文摘The interaction between dansyl-labeled pollen calmodulin (D-pCaM) and synthesized peptides was studied in the presence of Ca2+ by fluorescence spectra. It is Found that Gly/L-Ala --> D-Ala substitution in peptide chains caused great changes in their affinity for pCaM. Besides. our data provided evidence on the dissimilarity of different CaMs although they have highly-conserved structures. A preliminary study was carried out on the effects of CaM-binding peptides on cellular signal transduction, cell proliferation, showing the participation of CaM in cell functions mentioned above.
基金This research is supported by the National Natural Science Foundation of China (No. 70071040).
文摘In cells, the interactions of distinct signaling transduction pathways originating from cross-talkings between signaling molecules give rise to the formation of signaling transduction networks, which contributes to the changes (emergency) of kinetic behaviors of signaling system compared with single molecule or pathway. Depending on the known experimental data, we have constructed a model for complex cellular signaling transduction system, which is derived from signaling transduction of epidermal growth factor receptor in neuron. By the computational simulating methods, the self-adaptive controls of this system have been investigated. We find that this model exhibits a relatively stable selfadaptive system, especially to over-stimulation of agonist, and the amplitude and duration of signaling intermediates in it could be controlled by multiple self-adaptive effects, such as 'signal scattering', 'positive feedback', 'negative feedback' and 'B-Raf shunt'. Our results provide an approach to understanding the dynamic behaviors of complex biological systems.
基金kindly funded by National Natural Science Foundation of China(Grant No.31070752)in part supported by the National Basic Research Program(973 Program)(Nos 2011CB910204,2010CB529206 and 2010CB912702)+4 种基金Key Infectious Disease Project(No.2012ZX10002012-014)Research Program of Chinese Academy of Sciences(Nos.KSCX2-EW-R-04,KSCX2-YW-R-190 and 2011KIP204)National Natural Science Foundation of China(Grant No.30900272)Chinese Ministry for Science and Technology Grant(No.2008BAI64B01)the National High Technology Research and Development Program(863 Program)(No.2009AA02Z304).
文摘Studies on cell signaling pay more attention to spatial dynamics and how such diverse organization can relate to high order of cellular capabilities.To overview the specificity of cell signaling,we integrated human receptome data with proteome spatial expression profiles to systematically investigate the specificity of receptors and receptor-triggered transduction networks across 62 normal cell types and 14 cancer types.Six percent receptors showed cell-type-specific expression,and 4% signaling networks presented enriched cell-specific proteins induced by the receptors.We introduced a concept of“response context”to annotate the cell-type dependent signaling networks.We found that most cells respond similarly to the same stimulus,as the“response contexts”presented high functional similarity.Despite this,the subtle spatial diversity can be observed from the difference in network architectures.The architecture of the signaling networks in nerve cells displayed less completeness than that in glandular cells,which indicated cellular-context dependent signaling patterns are elaborately spatially organized.Likewise,in cancer cells most signaling networks were generally dysfunctional and less complete than that in normal cells.However,glioma emerged hyper-activated transduction mechanism in malignant state.Receptor ATP6AP2 and TNFRSF21 induced rennin-angiotensin and apoptosis signaling were found likely to explain the glioma-specific mechanism.This work represents an effort to decipher context-specific signaling network from spatial dimension.Our results indicated that although a majority of cells engage general signaling response with subtle differences,the spatial dynamics of cell signaling can not only deepen our insights into different signaling mechanisms,but also help understand cell signaling in disease.
基金supported over the past couple of years by the Deutsche Forschungsge-meinschaftthe Gemeinnützige Hertie-Stiftung+1 种基金the Well-come Trustthe Deutsche Akademische Austauschdienst
文摘Cyclic ADP-ribose (cADPR) is a universal Ca2+ mobilizing second messenger in many different cell types and organisms. cADPR activates Ca2+ release from endo/sarcoplasmic reticulum via ryanodine receptors. In addition, Ca2+ entry secondary to Ca2+ depletion is at least one of the mechanisms in which cADPR triggers Ca2+ inflow, too. Analogues of cADPR have been prepared by chemical and chemo-enzymatic routes. Most of the analogues were analyzed for biological activity in intact or permeabilized Jurkat T cells (a human T-lymphoma cell line). As a systematic approach, analogues were grouped according to alterations in the base, the northern ribose, the southern ribose, the pyrophosphate backbone, or in complex modifications, comprising more than one part of the molecule. Biological activity of the analogues is reviewed, with special emphasis on Jurkat T cells.