Receptor regulation of G protein palmitoylation.
Receptor regulation of G protein palmitoylation.
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G 蛋白棕榈酰化的受体调节。
DOI：
10.1042/bst0230156
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发表时间：
1995
影响因子：
3.9
通讯作者：
Muntz,KH
中科院分区：
文献类型：
--
作者：
Mumby,SM;Muntz,KH
G蛋白的一个主要作用是将细胞外信使与细胞内效应系统偶联。当被受体激活时，异源三聚体G蛋白解离成与GTP结合的a亚单位和a/3y亚单位复合体，这两个亚单位都能够调节效应器的活动[L]。这些G蛋白位于质膜的内面，在那里它们能够与跨膜的受体和效应器相互作用。信号转导G蛋白与膜的相互作用的分子基础还不是很清楚，因为它们缺乏清晰的疏水结构域，这些结构域有望促进与脂质双层的相互作用。G蛋白亚基的共价脂质修饰似乎有助于膜结合和与信号转导系统的其他组件的相互作用[2]。Y亚基在其C-末端被异丙烯化和羧甲基化。这些修饰有助于与/3y复合体与膜结合，对于Py与亚基、受体和效应器分子的高亲和力相互作用是必不可少的[3-51]。亚基的α；亚家族的成员被肉豆蔻酸酰胺不可逆地修饰--连接到N-末端甘氨酸残基(Gly-2)[6-91。肉豆蔻酰化增加了形成因子和效应子的亲和力，并在膜定位中发挥作用[7，10-121]。棕榈酸酯是被鉴定的最新修饰，这种脂肪酸被发现与几个α亚基有关[13-171]。大多数a亚家族成员都被肉豆蔻酸酯和棕榈酸酯(推测分别位于Gly-2和Cys-3)所修饰[131]。棕榈酰化的可逆性使其成为一个值得研究的令人兴奋的修饰，因为它可能在信号转导中发挥调节作用。鸟嘌呤核苷酸调节的信号转导最典型的例子之一是激素敏感的腺苷环化酶系统。由效应酶产生的第二信使环状AMP受到G蛋白的双重刺激和抑制控制，称为G和GI[11,181]。刺激腺苷环化酶的受体通过G_1偶联到酶上，而抑制性受体则通过G_i与酶相互作用。动态感
A major role of G proteins is to couple extracellular messengers to intracellular effector systems. Upon activation by receptor, a heterotrimeric G protein dissociates into a GTP-bound a subunit and a/3y subunit complex, both of which are able to modulate the activity of effectors [l]. These G proteins are positioned at the inner face of the plasma membrane where they are able to interact with membrane-spanning receptors and effectors. The molecular basis for interaction of signal-transducing G proteins with the membrane is not well understood as they lack clear hydrophobic domains which would be anticipated to promote interactions with the lipid bilayer. Covalent lipid modifications of G protein subunits appear to facilitate membrane association and interaction with other components of the signal-transduction systems [2]. The y subunits are prenylated and carboxymethylated at their C-termini. These modifications facilitate association with the/3y complex with membranes and are indispensable for high-affinity interactions of Py with a subunits, receptor, and effector molecules [3-51. Members of the a; subfamily of a subunits are irreversibly modified by myristate amide-linked to the N-terminal glycine residue (Gly-2)[6-91. Myristoylation increases the affinity of a for By and effector and also plays a role in membrane localization [7, 10-121. Palmitate is the most recent modification to be identified and this fatty acid is found linked to several a subunits [13-171. Most members of the a, subfamily are tandemly modified by both myristate and palmitate (presumably at Gly-2 and Cys-3 respectively)[131. The reversibility of palmitoylation makes it an exciting modification to study since it could potentially serve a regulatory role in signal transduction. One of the best-characterized examples of guanine nucleotide-regulated signal transduction is the hormone-sensitive adenylate cyclase system. Production of the second messenger, cyclic AMP, by the effector enzyme is under dual stimulatory and inhibitory control by G proteins termed G, and GI [11,181. Receptors that stimulate adenylate cyclase are coupled to the enzyme by G,, whereas inhibitory receptors interact with Gi. The dynamic