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Heineke J, Molkentin JD Regulation of cardiac hypertrophy by intracellular signalling pathways. Nat Rev Mol Cell Biol 2006 7:589-600 The mammalian heart is a dynamic organ that can grow and change to accommodate alterations in its workload. During development and in response to physiological stimuli or pathological insults, the heart undergoes hypertrophic enlargement, which is characterized by an increase in the size of individual cardiac myocytes. Recent findings in genetically modified animal models implicate important intermediate signal-transduction pathways in the coordination of heart growth following physiological and pathological stimulation. 哺乳动物的心脏是一个动力器官，它能够随着工作负荷的增减而进行适应性的改变。在发育过程中，及对生理性刺激或病理性损伤的反应过程中，心脏会经历一个肥大性扩大过程，主要表现为单个心肌细胞体积的增加。在最近的研究工作中发现给予经遗传修饰的模型动物以生理性或病理性刺激后，几条重要的信号传递途径交联对话，共同参与了心脏肥大过程。 Xin HB, Rogers K, Qi Y, Kanematsu T, Fleischer S Three amino acid residues determine selective binding of FK506-binding protein 12.6 to the cardiac ryanodine receptor. J Biol Chem 1999 274:15315-15319 FK506-binding protein FKBP12 has been found to be associated with the skeletal muscle ryanodine receptor RyR1 calcium release channel , whereas FKBP12.6, a novel isoform of FKBP, is selectively associated with the cardiac ryanodine receptor RyR2 . For both RyRs, the stoichiometry is 4 FKBP/RyR. Although FKBP12.6 differs from FKBP12 by only 18 of 108 amino acids, FKBP12.6 selectively binds to RyR2 and exchanges with bound FKBP12.6 of RyR2, whereas both FKBP isoforms bind to RyR1 and exchange with bound FKBP12 of RyR1. To assess the amino acid residues of FKBP12.6 that are critical for selective binding to RyR2, the residues of FKBP12.6 that differ with FKBP12 were mutated to the respective residues of FKBP12. RyR2 of cardiac sarcoplasmic reticulum, prelabeled by exchange with [35S]FKBP12.6, was used as assay system for binding/exchange with the mutants. The triple mutant Q31E/N32D/F59W of FKBP12.6 was found to lack selective binding to the cardiac RyR2, co