Interaction of 14-3-3 protein with regulator of G protein signaling 7 is dynamically regulated by tumor necrosis factor-α
Interaction of 14-3-3 protein with regulator of G protein signaling 7 is dynamically regulated by tumor necrosis factor-α
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DOI：
10.1074/jbc.m200859200
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发表时间：
2002-09-06
影响因子：
4.8
通讯作者：
Kim, E
中科院分区：
文献类型：
--
作者：
Benzing, T;Köttgen, M;Kim, E
G蛋白信号（RGS）的调节因子（regulatory of G protein signaling， RGS）是一个具有保守RGS结构域的蛋白家族，其结构域类似于120个氨基酸，可加速激活的Galpha(i)和Galpha(q)亚基的内在GTP水解。14-3-3蛋白与RGS蛋白亚群磷酸化依赖性相互作用抑制其体外gtpase加速活性。14-3-3与RGS7的抑制相互作用需要RGS7的434丝氨酸磷酸化。我们现在发现丝氨酸434的磷酸化是由tnf - α动态调节的。tnf - α刺激细胞可瞬间降低RGS7丝氨酸434的磷酸化，从而消除14-3-3的抑制相互作用。研究了14-3-3对非洲爪蟾卵母细胞中G蛋白偶联内向纠偏K+通道（GIRKs）失活动力学的影响。14-3-3抑制野生型RGS7的功能，但对不结合14-3-3的RSG7（P436R）和RGS4均无抑制作用。我们的发现首次证明细胞外信号可以通过调节RGS蛋白与14-3-3的相互作用来调节RGS蛋白的活性。
Regulators of G protein signaling (RGS) constitute a family of proteins with a conserved RGS domain of similar to 120 amino acids that accelerate the intrinsic GTP hydrolysis of activated Galpha(i) and Galpha(q) subunits. The phosphorylation-dependent interaction of 14-3-3 proteins with a subset of RGS proteins inhibits their GTPase-accelerating activity in vitro. The inhibitory interaction between 14-3-3 and RGS7 requires phosphorylation of serine 434 of RGS7. We now show that phosphorylation of serine 434 is dynamically regulated by TNF-alpha. Cellular stimulation by TNTF-alpha transiently decreased the phosphorylation of serine 434 of RGS7, abrogating the inhibitory interaction with 14-3-3. We examined the effect of 14-3-3 on RGS-mediated deactivation kinetics of G protein-coupled inwardly rectifying K+ channels (GIRKs) in Xenopus oocytes. 14-3-3 inhibited the function of wild-type RGS7, but not that of either RSG7(P436R) or RGS4, two proteins that do not bind 14-3-3. Our findings are the first evidence that extracellular signals can modulate the activity of RGS proteins by regulating their interaction with 14-3-3.