SUBSTRATE PHOSPHORYLATION CAN INHIBIT PROTEOLYSIS BY TRYPSIN-LIKE ENZYMES
SUBSTRATE PHOSPHORYLATION CAN INHIBIT PROTEOLYSIS BY TRYPSIN-LIKE ENZYMES
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DOI：
10.1016/0003-9861(89)90220-8
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发表时间：
1989-08-01
影响因子：
3.9
通讯作者：
WENNOGLE, LP
中科院分区：
文献类型：
--
作者：
BENOREPARSONS, M;SEIDAH, NG;WENNOGLE, LP
底物磷酸化对胰蛋白酶样酶的蛋白水解裂解的敏感性的影响进行了研究，使用模型七肽Leu-Arg-Arg-Ala-Ser-Leu-Gly，代表丙酮酸激酶的内源性磷酸化位点的肽。丝氨酸5的磷酸化改变了两种蛋白酶，胰蛋白酶和大鼠血浆激肽释放酶，这两种蛋白酶在精氨酸3和丙氨酸4之间裂解的蛋白水解动力学。在酪蛋白酶的情况下，磷酸化降低切割率47倍。在大鼠血浆激肽释放酶的情况下，磷酸化减少蛋白水解13倍。磷酸化导致了明显的重定向的优先网站从精氨酸3到精氨酸2。由于类似于该模型肽的序列通常存在于球状蛋白的暴露结构域中，并且由于这些区域易受磷酸化和蛋白酶攻击，因此结果表明底物磷酸化可能选择性地影响蛋白质加工和周转。
The effect of substrate phosphorylation on the susceptibility to proteolytic cleavage by trypsin-like enzymes was investigated using the model heptapeptide Leu-Arg-Arg-Ala-Ser-Leu-Gly, a peptide representing the endogenous phosphorylation site of pyruvate kinase. Phosphorylation of Ser 5 altered the kinetics of proteolysis by two proteases, trypsin and rat plasma kallikrein, both of which cleaved between Arg 3 and Ala 4. In the case of tyrpsin, phosphorylation decreased the rate of cleavage 47-fold. In the case of rat plasma kallikrein, phosphorylation decreased proteolysis 13-fold. Phosphorylation resulted in an apparent redirection of the preferential site from Arg 3 to Arg 2. Because sequences analogous to this model peptide are commonly found in exposed domains of globular proteins, and since these regions are susceptible to both phosphorylation and protease attack, the results indicate that substrate phosphorylation may selectively influence protein processing and turnover.