Protein phosphatase 1--targeted in many directions.
Protein phosphatase 1--targeted in many directions.
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作者：
P. Cohen
蛋白磷酸酶1（PP1）是一种主要的真核生物蛋白质丝氨酸/苏氨酸磷酸酶，它通过其催化亚基（PP1c）与50多种已确定的或假定的调节亚基相互作用，调节多种多样的细胞功能。这些调节亚基大多将PP1c靶向特定的亚细胞位置，并通过一个短的保守结合基序——RVxF基序（其前面通常还有更多的碱性残基）与PP1c表面的一个小的疏水凹槽相互作用。较弱的相互作用随后可能以多种方式增强结合并调节PP1的活性/特异性。一些假定的靶向亚基不具有RVxF基序，但仍然与PP1c的同一区域相互作用。此外，一些“调节”蛋白与PP1c结合，但不具有将它们靶向特定位置的结构域。大多数是PP1c的强效抑制剂，并且至少具有两个与PP1c相互作用的位点，其中一个与RVxF基序相同或相似。PP1c对细胞外和细胞内信号的响应调节主要通过靶向亚基的水平、构象或磷酸化状态的变化来实现。对PP1c复合物作用模式的理解可能有助于开发针对特定PP1c复合物的药物，从而调节非常有限的一组蛋白质的磷酸化状态。
Protein phosphatase 1 (PP1) is a major eukaryotic protein serine/threonine phosphatase that regulates an enormous variety of cellular functions through the interaction of its catalytic subunit (PP1c) with over fifty different established or putative regulatory subunits. Most of these target PP1c to specific subcellular locations and interact with a small hydrophobic groove on the surface of PP1c through a short conserved binding motif--the RVxF motif--which is often preceded by further basic residues. Weaker interactions may subsequently enhance binding and modulate PP1 activity/specificity in a variety of ways. Several putative targeting subunits do not possess an RVxF motif but nevertheless interact with the same region of PP1c. In addition, several 'modulator' proteins bind to PP1c but do not possess a domain targeting them to a specific location. Most are potent inhibitors of PP1c and possess at least two sites for interaction with PP1c, one of which is identical or similar to the RVxF motif. Regulation of PP1c in response to extracellular and intracellular signals occurs mostly through changes in the levels, conformation or phosphorylation status of targeting subunits. Understanding of the mode of action of PP1c complexes may facilitate development of drugs that target particular PP1c complexes and thereby modulate the phosphorylation state of a very limited subset of proteins.