Yaffe M B, Elia A E
Center for Cancer Research E18-580, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
Curr Opin Cell Biol. 2001 Apr;13(2):131-8. doi: 10.1016/s0955-0674(00)00189-7.
Phosphorylation of proteins on serine and threonine residues has traditionally been viewed as a means to allosterically regulate catalytic activity. Research within the past five years, however, has revealed that serine/threonine phosphorylation can also directly result in the formation of multimolecular signaling complexes through specific interactions between phosphoserine/threonine (pSer/Thr)-binding modules and phosphorylated sequence motifs. pSer/Thr-binding proteins and domains currently include 14-3-3, WW domains, forkhead-associated domains, and, tentatively, WD40 repeats and leucine-rich regions. It seems likely that additional modules will be found in the future. The amino acid sequences recognized by these pSer/Thr-binding modules show partial overlap with the optimal phosphorylation motifs for different protein kinase subfamilies, allowing the formation of specific signaling complexes to be controlled through combinatorial interactions between particular upstream kinases and a particular binding module. The structural basis for pSer/Thr binding differs dramatically between 14-3-3 proteins, WW domains and forkhead-associated domains, suggesting that their pSer/Thr binding function was acquired through convergent evolution.
蛋白质丝氨酸和苏氨酸残基的磷酸化传统上被视为变构调节催化活性的一种方式。然而，过去五年的研究表明，丝氨酸/苏氨酸磷酸化也可通过磷酸丝氨酸/苏氨酸（pSer/Thr）结合模块与磷酸化序列基序之间的特异性相互作用直接导致多分子信号复合物的形成。目前，pSer/Thr结合蛋白和结构域包括14-3-3、WW结构域、叉头相关结构域，以及暂时确定的WD40重复序列和富含亮氨酸的区域。未来可能会发现更多的模块。这些pSer/Thr结合模块识别的氨基酸序列与不同蛋白激酶亚家族的最佳磷酸化基序部分重叠，使得特定信号复合物的形成能够通过特定上游激酶与特定结合模块之间的组合相互作用来控制。14-3-3蛋白、WW结构域和叉头相关结构域之间，pSer/Thr结合的结构基础差异很大，这表明它们的pSer/Thr结合功能是通过趋同进化获得的。
