Sequence-specific and phosphorylation-dependent proline isomerization: A potential mitotic regulatory mechanism
Sequence-specific and phosphorylation-dependent proline isomerization: A potential mitotic regulatory mechanism
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DOI：
10.1126/science.278.5345.1957
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发表时间：
1997-12-12
期刊：
影响因子：
56.9
通讯作者：
Lu, KP
中科院分区：
文献类型：
--
作者：
Yaffe, MB;Schutkowski, M;Lu, KP
Pin1是一种必需的、保守的有丝分裂肽基-脯氨基异构酶(PPlase)，它不同于另外两个常规PPlase家族的成员，即亲环素和FKBPs(FK-506结合蛋白)。作为对它们在有丝分裂过程中的磷酸化的反应，Pin1结合并调节一组高度保守的蛋白质的成员；这些蛋白质与有丝分裂特异的单抗MPM-2识别的抗原重叠。Pin1是一种依赖于磷酸化的PPlase，它能识别有丝分裂蛋白中存在的磷酸丝氨酸-脯氨酸或磷酸苏氨酸-脯氨酸键。Pin1和MPM-2都选择了相似的磷酸化丝氨酸-脯氨酸多肽，为Pin1和MPM-2抗原之间的特异性相互作用提供了基础。与未磷酸化的多肽相比，Pin1优先异构化的脯氨酸残基前面有磷酸化的丝氨酸或苏氨酸，选择性高达1300倍。因此，Pin1可能通过催化序列特异性和磷酸化依赖的脯氨酸异构化来调节有丝分裂进程。
Pin1 is an essential and conserved mitotic peptidyl-prolyl isomerase (PPlase) that is distinct from members of two other families of conventional PPlases, cyclophilins and FKBPs (FK-506 binding proteins). In response to their phosphorylation during mitosis, Pin1 binds and regulates members of a highly conserved set of protein; that overlaps with antigens recognized by the mitosis-specific monoclonal antibody MPM-2. Pin1 is here shown to be a phosphorylation-dependent PPlase that specifically recognizes the phosphoserine-proline or phosphothreonine-proline bonds present in mitotic phosphoproteins. Both Pin1 and MPM-2 selected similar phosphorylated serine-proline-containing peptides, providing the basis for the specific interaction between Pin1 and MPM-2 antigens. Pin1 preferentially isomerized proline residues preceded by phosphorylated serine or threonine with up to 1300-fold selectivity compared with unphosphorylated peptides. Pin1 may thus regulate mitotic progression by catalyzing sequence-specific and phosphorylation-dependent proline isomerization.