PHOSDUCIN INHIBITS RECEPTOR PHOSPHORYLATION BY THE BETA-ADRENERGIC-RECEPTOR KINASE IN A PKA-REGULATED MANNER
PHOSDUCIN INHIBITS RECEPTOR PHOSPHORYLATION BY THE BETA-ADRENERGIC-RECEPTOR KINASE IN A PKA-REGULATED MANNER
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DOI：
10.1016/0014-5793(94)80302-1
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发表时间：
1994-04-25
期刊：
影响因子：
3.5
通讯作者：
LOHSE, MJ
中科院分区：
文献类型：
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作者：
HEKMAN, M;BAUER, PH;LOHSE, MJ
β-肾上腺素能受体的同源或受体特异性脱敏被认为是由β-肾上腺素能受体激酶（β ARK）介导的受体磷酸化触发的。受体激活后，胞质 BARK 可能通过与 G 蛋白 β γ 亚基结合而易位到膜上。使用重构到磷脂囊泡中的纯化蛋白，我们在此表明这种结合过程可以被磷酸蛋白抑制，磷酸蛋白是一种胞质蛋白，最近被描述为 G 蛋白介导的信号传导的调节剂。 Phosducin 似乎可以非常有效地与 G 蛋白 β γ 亚基的 β ARK 结合。磷酸化蛋白对受体磷酸化的这些抑制作用在磷酸化蛋白激酶A磷酸化后被拮抗。有人提出，磷酸化蛋白可能充当同源β-肾上腺素能受体脱敏的调节剂。
Homologous or receptor-specific desensitization of beta-adrenergic receptors is thought to be triggered by receptor phosphorylation mediated by the beta-adrenergic receptor kinases (beta ARK). Upon receptor activation, cytosolic BARK translocates to the membrane, probably by binding to G-protein beta gamma-subunits. Using the purified proteins reconstituted into phospholipid vesicles we show here that this binding process can be inhibited by phosducin, a cytosolic protein that has recently been described as a regulator of G-protein-mediated signalling. Phosducin appears to complete very effectively with beta ARK for the G-protein beta gamma-subunits. These inhibitory effects of phosducin on receptor phosphorylation are antagonized following phosphorylation of phosducin by protein kinase A. It is proposed that phosducin may act as a regulator of homologous beta-adrenergic receptor desensitization.