A site of interaction between pleckstrin's PH domains and G(beta gamma)
A site of interaction between pleckstrin's PH domains and G(beta gamma)
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DOI：
10.1016/s0167-4889(96)00109-7
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发表时间：
1996-12-12
影响因子：
5.1
通讯作者：
Brass, LF
中科院分区：
文献类型：
--
作者：
Abrams, CS;Zhao, W;Brass, LF
Pleckstrin 是血小板和中性粒细胞中发现的蛋白激酶 C 的 40 kDa 底物。根据其序列，pleckstrin 包含两个最近描述的 PH 结构域，这些结构域被认为是磷脂酰 4,5-二磷酸 (PIP2) 和/或 G 蛋白 β γ 异二聚体 (G(β γ)) 的结合基序。在目前的研究中，我们通过将 pleckstrin 融合蛋白与人血小板裂解物一起孵育，研究了 pleckstrin 和 G(beta gamma) 之间的相互作用。在此分析中，来自 pleckstrin 的 N 端和 C 端 PH 结构域在体外均结合 G(beta gamma)，含有少至 C 端 pleckstrin PH 结构域前 30 个残基的肽也是如此。在该区域引入点突变（类似于导致小鼠 X 连锁免疫缺陷病 (XID) 的 Btk PH 结构域突变）会极大地破坏这种相互作用。我们提出 pleckstrin 可能与 G(beta gamma) 相互作用，并且这种相互作用的一个潜在位点涉及 pleckstrin C 端 PH 结构域的前 30 个残基。
Pleckstrin is a 40 kDa substrate for protein kinase C found in platelets and neutrophils. Based upon its sequence, pleckstrin contains two of the recently-described PH domains that are thought to be binding motifs for phosphatidyl 4,5-bisphosphate (PIP2) and/or G protein beta gamma heterodimers (G(beta gamma)). In the present studies we have examined the interaction between pleckstrin and G(beta gamma) by incubating pleckstrin fusion proteins with lysates from human platelets. In this analysis, both the N-terminal and C-terminal PH domains from pleckstrin bound G(beta gamma) in vitro, as did peptides containing as little as the first 30 residues of the C-terminal pleckstrin PH domain. Introduction of a point mutation into this region, analogous to the mutation in the Btk PH domain that causes X-linked immunodeficiency disease (XID) in mice, dramatically disrupted this interaction. We propose that pleckstrin may interact with G(beta gamma) and that one potential site for this interaction involves the first 30 residues of pleckstrin's C-terminal PH domain.