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首页> 外文期刊>Molecular and Cellular Biology >Spatial and Temporal Regulation of Focal Adhesion Kinase Activity in Living Cells
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Spatial and Temporal Regulation of Focal Adhesion Kinase Activity in Living Cells

机译：活细胞中黏着斑激酶活性的时空调控

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Focal adhesion kinase (FAK) is an essential kinase that regulates developmental processes and functions in the pathology of human disease. An intramolecular autoinhibitory interaction between the FERM and catalytic domains is a major mechanism of regulation. Based upon structural studies, a fluorescence resonance energy transfer (FRET)-based FAK biosensor that discriminates between autoinhibited and active conformations of the kinase was developed. This biosensor was used to probe FAK conformational change in live cells and the mechanism of regulation. The biosensor demonstrates directly that FAK undergoes conformational change in vivo in response to activating stimuli. A conserved FERM domain basic patch is required for this conformational change and for interaction with a novel ligand for FAK, acidic phospholipids. Binding to phosphatidylinositol 4,5-bisphosphate (PIP2)-containing phospholipid vesicles activated and induced conformational change in FAK in vitro, and alteration of PIP2 levels in vivo changed the level of activation of the conformational biosensor. These findings provide direct evidence of conformational regulation of FAK in living cells and novel insight into the mechanism regulating FAK conformation.
机译：粘着斑激酶（FAK）是一种必需的激酶，可调节人类疾病病理过程中的发育过程和功能。 FERM和催化域之间的分子内自抑制相互作用是主要的调节机制。基于结构研究，开发了一种基于荧光共振能量转移（FRET）的FAK生物传感器，该传感器可区分激酶的自抑制构象和活性构象。该生物传感器用于探测活细胞中FAK的构象变化及其调控机制。该生物传感器直接证明，FAK在体内响应激活刺激而发生构象变化。对于这种构象变化以及与FAK的新配体酸性磷脂相互作用，需要保守的FERM结构域基本补丁。结合磷脂酰肌醇4,5-二磷酸（PIP2）的磷脂囊泡在体外激活并诱导FAK的构象变化，体内PIP2水平的改变也改变了构象生物传感器的激活水平。这些发现为活细胞中FAK的构象调节提供了直接证据，并为调节FAK构象的机制提供了新颖的见解。

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