Burgaya F, Toutant M, Studler J M, Costa A, Le Bert M, Gelman M, Girault J A
INSERM U 114, Chaire de Neuropharmacologie, Collège de France, 11 place Marcelin Berthelot, 75231 Paris cedex 05, France.
J Biol Chem. 1997 Nov 7;272(45):28720-5. doi: 10.1074/jbc.272.45.28720.
pp125 focal adhesion kinase (FAK), a cytoplasmic tyrosine kinase transducing signals initiated by integrin engagement and G protein-coupled receptors, is highly expressed in brain. FAK from brain had a higher molecular weight and an increased autophosphorylation activity, than from other tissues. In addition to a 9-base insertion in the 3'-coding region, which defines FAK+, rat striatal FAK mRNAs contained several additional short exons, coding for peptides of 28, 6, and 7 residues, respectively (termed boxes 28, 6, and 7), surrounding the autophosphorylated Tyr-397. In transfected COS 7 cells, the presence of boxes 6 and 7 conferred an increased overall tyrosine phosphorylation, a higher phosphorylation of Tyr-397 assessed with a phosphorylation state-specific antibody, and a more active autophosphorylation in immune precipitates. The presence of box 28 did not alter further these parameters. Two-dimensional phosphopeptide maps of hippocampal FAK were identical to those of FAK+6,7. The presence of the various exons did not alter the interaction of FAK with c-Src, n-Src, or Fyn. Thus, several splice isoforms of FAK are preferentially expressed in rat brain, some of which have an increased autophosphorylation activity, suggesting that FAK may have specific properties in neurons.
第125页 粘着斑激酶（FAK）是一种细胞质酪氨酸激酶，可转导由整合素结合和G蛋白偶联受体引发的信号，在脑中高度表达。来自脑的FAK比来自其他组织的FAK具有更高的分子量和增强的自磷酸化活性。除了在3'-编码区有一个9碱基的插入（定义为FAK+）外，大鼠纹状体FAK mRNA还包含几个额外的短外显子，分别编码28、6和7个残基的肽段（称为框28、框6和框7），围绕着自磷酸化的Tyr-397。在转染的COS 7细胞中，框6和框7的存在导致总体酪氨酸磷酸化增加，用磷酸化状态特异性抗体评估的Tyr-397磷酸化水平更高，并且免疫沉淀物中的自磷酸化更活跃。框28的存在并未进一步改变这些参数。海马FAK的二维磷酸肽图谱与FAK+6,7的图谱相同。各种外显子的存在并未改变FAK与c-Src、n-Src或Fyn的相互作用。因此，FAK的几种剪接异构体在大鼠脑中优先表达，其中一些具有增强的自磷酸化活性，这表明FAK在神经元中可能具有特定特性。
