CLONING OF A COMPLEMENTARY-DNA FOR A PROTEIN-TYROSINE KINASE THAT SPECIFICALLY PHOSPHORYLATES A NEGATIVE REGULATORY SITE OF P60C-SRC
CLONING OF A COMPLEMENTARY-DNA FOR A PROTEIN-TYROSINE KINASE THAT SPECIFICALLY PHOSPHORYLATES A NEGATIVE REGULATORY SITE OF P60C-SRC
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DOI：
10.1038/351069a0
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发表时间：
1991-05-02
期刊：
影响因子：
64.8
通讯作者：
NAKAGAWA, H
中科院分区：
文献类型：
--
作者：
NADA, S;OKADA, M;NAKAGAWA, H
原癌基因产物p60 c-src的蛋白酪氨酸激酶活性受靠近C末端的酪氨酸残基酪氨酸527的磷酸化负调节（参考文献1-11）。 磷酸化可能是由一种迄今尚未鉴定的酪氨酸激酶催化的，不同于p60 c-src（参考文献7）。 最近，我们从新生大鼠脑中纯化了一种特异性磷酸化p60 c-src酪氨酸527的蛋白酪氨酸激酶8，12，13。 我们现在已经通过使用具有苯丙氨酸而不是酪氨酸527的突变体p60 c-src证实了这种酶的特异性，并克隆了编码该酶的互补DNA。 该酶类似于src家族的激酶，因为它在酪氨酸激酶结构域的上游具有两个保守区，Src同源区2和3。 然而，每个区域的氨基酸同一性不超过47%，并且该酶缺乏对应于p60 c-src的酪氨酸416和527的磷酸化位点，并且没有肉豆蔻酰化信号。 这些结果表明，该蛋白酪氨酸激酶可能是一种新型的酪氨酸激酶，它可能负调控p60 c-src。
THE protein-tyrosine kinase activity of the proto-oncogene product p60c-src is negatively regulated by the phosphorylation of a tyrosine residue close to the C terminus, tyrosine 527 (refs 1-11). The phosphorylation might be catalysed by a so-far-unidentified tyrosine kinase, distinct from p60c-src (ref. 7). Recently we purified a protein-tyrosine kinase that specifically phosphorylates tyrosine 527 of p60c-src from neonatal rat brain 8,12,13. We have now confirmed the specificity of this enzyme by using a mutant p60c-src that has a phenylalanine instead of tyrosine 527, and cloned a complementary DNA that encodes the enzyme. The enzyme is similar to kinases of the src family in that it has two conserved regions, Src-homology regions 2 and 3, upstream of a tyrosine kinase domain. The amino-acid identity of each region is no more than 47%, however, and the enzyme lacks phosphorylation sites corresponding to tyrosines 416 and 527 of p60c-src and has no myristylation signal. These results suggest that this protein-tyrosine kinase, which might negatively regulate p60c-src, represents a new type of tyrosine kinase.