Activation of the oncogenic potential of the avian cellular src protein by specific structural alteration of the carboxy terminus.

Activation of the oncogenic potential of the avian cellular src protein by specific structural alteration of the carboxy terminus.
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通过羧基末端的特定结构改变激活禽细胞 src 蛋白的致癌潜力。

DOI:
10.1002/j.1460-2075.1987.tb02512.x
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发表时间:
1987
期刊:
The EMBO journal
影响因子:
--
通讯作者:
Parsons,JT
Parsons,JT
中科院分区:
--
文献类型:
--
作者:
Reynolds,AB;Vila,J;Lansing,TJ;Potts,WM;Weber,MJ;Parsons,JT

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酪氨酸磷酸化在酪氨酸蛋白激酶活性调节中的作用进行了研究,使用定点突变,以改变存在于禽pp 60 c-src的C末端的三个酪氨酸残基的结构和环境。将Tyr 527改变为Phe或Ser的突变激活体内酪氨酸蛋白激酶活性并诱导培养物中鸡细胞的细胞转化。相反,c-src中511或519位酪氨酸残基的改变不诱导转化或体内酪氨酸蛋白激酶活性。琥珀色突变通过诱导c-src蛋白在残基518或523处的过早终止而改变pp 60 c-src C末端的结构,也诱导形态学转化并增加体内酪氨酸磷酸化,而通过残基530处的链终止去除c-src的最后四个残基不会改变所得c-src蛋白的激酶活性或生物活性。我们从这些研究中得出结论,C-末端的改变,要么删除或取代酪氨酸527激活c-src蛋白,导致细胞转化和增加体内酪氨酸蛋白激酶活性。图像
The role of tyrosine phosphorylation in the regulation of tyrosine protein kinase activity was investigated using site-directed mutagenesis to alter the structure and environment of the three tyrosine residues present in the C terminus of avian pp60c-src. Mutations that change Tyr 527 to Phe or Ser activate in vivo tyrosine protein kinase activity and induce cellular transformation of chicken cells in culture. In contrast, alterations of tyrosine residues present at positions 511 or 519 in c-src do not induce transformation or in vivo tyrosine protein kinase activity. Amber mutations, which alter the structure of the pp60c-src C terminus by inducing premature termination of the c-src protein at either residue 518 or 523 also induce morphological transformation and increase in vivo tyrosine phosphorylation, whereas removal of the last four residues of c-src by chain termination at residue 530 does not alter the kinase activity or the biological activity of the resultant c-src protein. We conclude from these studies that C-terminal alterations which either remove or replace Tyr 527 serve to activate the c-src protein resulting in cellular transformation and increased in vivo tyrosine protein kinase activity. Images
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