Introduction A disintegrin and metalloproteinase 33（ADAM33）has been identified as a susceptibility gene for asthma<sup>[1]</sup>,In particular,ADAM33 mRNA is highly expressed in airway smooth muscle cell...Introduction A disintegrin and metalloproteinase 33（ADAM33）has been identified as a susceptibility gene for asthma<sup>[1]</sup>,In particular,ADAM33 mRNA is highly expressed in airway smooth muscle cells（ASMCs）and the level of soluble ADAM33（sADAM33）is known to inversely correlate with lung function such as bronchial hyperresponsiveness（BHR）<sup>[2]</sup>that is ultimately determined by the mechanical behaviors of ASMCs.However,few have studied how sADAM33would affect ASMC mechanics.Here,we manipulated the expression of SADAM33 in展开更多
Introduction Cells can sense and respond to the mechanical microenvironment by converting forces into biochemical signals inside the cells,i.e.mechanotransduction<sup>[1-3]</sup>.Focal adhesions are the ma...Introduction Cells can sense and respond to the mechanical microenvironment by converting forces into biochemical signals inside the cells,i.e.mechanotransduction<sup>[1-3]</sup>.Focal adhesions are the major sites of interaction between a cell and its extracellular matrix（ECM）microenvironment,thus outside mechanical signals can be sensed at focal adhesions through transmembrane receptor integrins.In particular,it has been shown that matrix elasticity can control the cell fate<sup>[4]</sup>by modulating the interactions between ECM proteins and their receptor integrins<sup>[5,6]</sup>.For example,different rigidity of polyacrylamide（PA）gels can lead to different density of ECM ancho-展开更多
Introduction Hematogenous metastasis is the mainly leading cause of death in breast carcinoma patients.A better understanding of the underlying molecular and cellular mechanisms is crucial for the development of effec...Introduction Hematogenous metastasis is the mainly leading cause of death in breast carcinoma patients.A better understanding of the underlying molecular and cellular mechanisms is crucial for the development of effective treatment for metastatic breast cancer<sup>[</sup>1].It has been well established that cell adhesion and invasion is mediated by a variety of transmembrane proteins,including integrins,cadherins,selectins,and intercellular adhesion molecules.Among these adhesion molecules,the integrins and their downstream signaling pathways have been extensively studied<sup>[2]</sup>.On the other hand,the specific events determining tumor cell interactions with endo-展开更多
Notch proteins are transmembrane receptors which can transduce signals between cells.Upon binding to their ligands on the neighboring cells,notch receptors can be activated and undergo conformational changes which ena...Notch proteins are transmembrane receptors which can transduce signals between cells.Upon binding to their ligands on the neighboring cells,notch receptors can be activated and undergo conformational changes which enable their proteolysis by ADAM-family of metalloproteases<sup>[1]</sup>.The cleavage site of notch protein located on its hetrodimerizaton domain（HD）of the negative regulatory region（NRR）proximal to the N-terminal of the transmembrane helix.Recent crystal structures on several notch proteins<sup>[2-4]</sup>indicated that a series of three Lin12/Notch repeats（LNRs）wrap around the HD and bury the cleavage site to prevent it from proteolysis at the normal conditions without ligand binding.Studies indicated that notch/ligand binding may al-展开更多
Anti-Fas or Fas ligand can induce apoptosis whenthey bind Fas antigen on cell surfaces, and have potentialtherapeutic uses. But the disadvantage is obvious asnormal cells can also be killed. In this paper, weconstruct...Anti-Fas or Fas ligand can induce apoptosis whenthey bind Fas antigen on cell surfaces, and have potentialtherapeutic uses. But the disadvantage is obvious asnormal cells can also be killed. In this paper, weconstructed a fusion protein between the transmembraneand cytoplasmic domains of hfas and the HBD (hormonebinding domain) of hER (referred to as MfasER).Glioma cells transfeced with MfasER could be indued展开更多
基金supported by National Natural Science Foundation of China(11172340)Training Program for Hundreds of Distinguished Leading Scientists of ChongqingSpecialized Research Fund for the Doctoral Program of Higher Education of China(20120191120032)
文摘Introduction A disintegrin and metalloproteinase 33（ADAM33）has been identified as a susceptibility gene for asthma<sup>[1]</sup>,In particular,ADAM33 mRNA is highly expressed in airway smooth muscle cells（ASMCs）and the level of soluble ADAM33（sADAM33）is known to inversely correlate with lung function such as bronchial hyperresponsiveness（BHR）<sup>[2]</sup>that is ultimately determined by the mechanical behaviors of ASMCs.However,few have studied how sADAM33would affect ASMC mechanics.Here,we manipulated the expression of SADAM33 in
基金supported in part by NIH HL098472NSF CBET0846429
文摘Introduction Cells can sense and respond to the mechanical microenvironment by converting forces into biochemical signals inside the cells,i.e.mechanotransduction<sup>[1-3]</sup>.Focal adhesions are the major sites of interaction between a cell and its extracellular matrix（ECM）microenvironment,thus outside mechanical signals can be sensed at focal adhesions through transmembrane receptor integrins.In particular,it has been shown that matrix elasticity can control the cell fate<sup>[4]</sup>by modulating the interactions between ECM proteins and their receptor integrins<sup>[5,6]</sup>.For example,different rigidity of polyacrylamide（PA）gels can lead to different density of ECM ancho-
基金The financial supports provided,in whole or in part,by the National Natural Science Foundation of China(11272083)the New Century Excellent Talents Program in Chinese Universities(NCET09-0263)
文摘Introduction Hematogenous metastasis is the mainly leading cause of death in breast carcinoma patients.A better understanding of the underlying molecular and cellular mechanisms is crucial for the development of effective treatment for metastatic breast cancer<sup>[</sup>1].It has been well established that cell adhesion and invasion is mediated by a variety of transmembrane proteins,including integrins,cadherins,selectins,and intercellular adhesion molecules.Among these adhesion molecules,the integrins and their downstream signaling pathways have been extensively studied<sup>[2]</sup>.On the other hand,the specific events determining tumor cell interactions with endo-
基金supported by grants from Natural Science Foundations of China(31070827, 31222022,and 81161120424)the Knowledge Innovation Program of the Chinese Academy of Sciens
文摘Notch proteins are transmembrane receptors which can transduce signals between cells.Upon binding to their ligands on the neighboring cells,notch receptors can be activated and undergo conformational changes which enable their proteolysis by ADAM-family of metalloproteases<sup>[1]</sup>.The cleavage site of notch protein located on its hetrodimerizaton domain（HD）of the negative regulatory region（NRR）proximal to the N-terminal of the transmembrane helix.Recent crystal structures on several notch proteins<sup>[2-4]</sup>indicated that a series of three Lin12/Notch repeats（LNRs）wrap around the HD and bury the cleavage site to prevent it from proteolysis at the normal conditions without ligand binding.Studies indicated that notch/ligand binding may al-
文摘Anti-Fas or Fas ligand can induce apoptosis whenthey bind Fas antigen on cell surfaces, and have potentialtherapeutic uses. But the disadvantage is obvious asnormal cells can also be killed. In this paper, weconstructed a fusion protein between the transmembraneand cytoplasmic domains of hfas and the HBD (hormonebinding domain) of hER (referred to as MfasER).Glioma cells transfeced with MfasER could be indued
