The N2-Src neuronal splice variant of C-Src has altered SH3 domain ligand specificity and a higher constitutive activity than N1-Src.
The N2-Src neuronal splice variant of C-Src has altered SH3 domain ligand specificity and a higher constitutive activity than N1-Src.
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DOI：
10.1016/j.febslet.2015.05.033
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发表时间：
2015-07-08
期刊：
影响因子：
3.5
通讯作者：
Evans GJ
中科院分区：
文献类型：
--
作者：
Keenan S;Lewis PA;Wetherill SJ;Dunning CJ;Evans GJ
N2-Src是C-Src激酶的一种以前未表征的神经元剪接变体。通过C-Src的酪氨酸磷酸化被SH 3肽配体增强。理想的C-Src SH 3配体不增强N2-或N1-Src激酶的底物磷酸化。N2-Src在体外和细胞中比C-和N1-Src更有活性。N2-Src可能在大脑中有替代底物。N2-Src是普遍存在的C-Src酪氨酸激酶的神经元剪接变体，在其Src同源性3（SH 3）结构域中含有17个氨基酸的插入物。为了证实N2-Src的性质，我们直接在体外将其SH 3结构域特异性和激酶活性与C-和N1-Src进行比较。N2-和N1-Src具有类似的低亲和力磷酸化的基板含有典型的C-Src SH 3配体和突触素，一个既定的神经元基板C-Src。N2-Src在体外和细胞中也具有比N1-和C-Src更高的基础激酶活性，这可以通过减弱的分子内相互作用来解释。因此，N2-Src是一种高活性的激酶，可能磷酸化脑中C-Src的替代底物。
N2-Src is a previously uncharacterised neuronal splice variant of C-Src kinase. Tyrosine phosphorylation by C-Src is enhanced by SH3 peptide ligands. Ideal C-Src SH3 ligands do not enhance substrate phosphorylation by N2- or N1-Src kinase. N2-Src is more active than C- and N1-Src in vitro and in cells. N2-Src is likely to have alternative substrates in the brain. N2-Src is a poorly understood neuronal splice variant of the ubiquitous C-Src tyrosine kinase, containing a 17 amino acid insert in its Src homology 3 (SH3) domain. To characterise the properties of N2-Src we directly compared its SH3 domain specificity and kinase activity with C- and N1-Src in vitro. N2- and N1-Src had a similar low affinity for the phosphorylation of substrates containing canonical C-Src SH3 ligands and synaptophysin, an established neuronal substrate for C-Src. N2-Src also had a higher basal kinase activity than N1- and C-Src in vitro and in cells, which could be explained by weakened intramolecular interactions. Therefore, N2-Src is a highly active kinase that is likely to phosphorylate alternative substrates to C-Src in the brain.