Distinct functional roles of the two intracellular phosphatase like domains of the receptor-linked protein tyrosine phosphatases LCA and LAR.
Distinct functional roles of the two intracellular phosphatase like domains of the receptor-linked protein tyrosine phosphatases LCA and LAR.
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受体连接蛋白酪氨酸磷酸酶 LCA 和 LAR 的两个细胞内磷酸酶样结构域具有不同的功能作用。
DOI：
10.1002/j.1460-2075.1990.tb07415.x
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Saito,H
中科院分区：
文献类型：
--
作者：
Streuli,M;Krueger,NX;Thai,T;Tang,M;Saito,H
蛋白酪氨酸磷酸化受蛋白酪氨酸激酶和蛋白酪氨酸磷酸酶(PTPase)的调节。最近，一个PTPase家族的结构已被描述。为了研究受体连接的PTPase的结构与功能的关系，我们分析了受体连接的PTPase、LCA和LAR细胞质区域的缺失和点突变的影响。我们证明了两个结构域中的第一个结构域本身具有酶活性，并且LCA和LAR的第一个结构域中的一个半胱氨酸残基是活性所绝对需要的。第二个PTPase类结构域在使用各种底物时不具有可检测到的催化活性，但第二个结构域中的序列影响底物特异性。评估了位于LAR第一结构域关键半胱氨酸残基周围的10个高度保守的氨基酸残基的功能意义。在大多数位置，任何替换都会严重降低酶的活性，而其他被测试位置的错义突变可以在不同程度上被容忍，这取决于氨基酸的替换。推测这段氨基酸可能是PTPase催化中心的一部分。
Protein tyrosine phosphorylation is regulated by both protein tyrosine kinases and protein tyrosine phosphatases (PTPases). Recently, the structures of a family of PTPases have been described. In order to study the structure‐function relationships of receptor‐linked PTPases, we analyzed the effects of deletion and point mutations within the cytoplasmic region of the receptor‐linked PTPases, LCA and LAR. We show that the first of the two domains has enzyme activity by itself, and that one cysteine residue in the first domain of both LCA and LAR is absolutely required for activity. The second PTPase like domains do not have detectable catalytic activity using a variety of substrates, but sequences within the second domains influence substrate specificity. The functional significance of a stretch of 10 highly conserved amino acid residues surrounding the critical cysteine residue located in the first domain of LAR was assessed. At most positions, any substitution severely reduced enzyme activity, while missense mutations at the other positions tested could be tolerated to varying degrees depending on the amino acid substitution. It is suggested that this stretch of amino acids may be part of the catalytic center of PTPases.