Willardson Barry M, Howlett Alyson C
Department of Chemistry and Biochemistry, C-100 BNSN, Brigham Young University Provo, Utah 84602, USA.
Cell Signal. 2007 Dec;19(12):2417-27. doi: 10.1016/j.cellsig.2007.06.013. Epub 2007 Jun 28.
Members of the phosducin gene family were initially proposed to act as down-regulators of G protein signaling by binding G protein betagamma dimers (Gbetagamma) and inhibiting their ability to interact with G protein alpha subunits (Galpha) and effectors. However, recent findings have over-turned this hypothesis by showing that most members of the phosducin family act as co-chaperones with the cytosolic chaperonin complex (CCT) to assist in the folding of a variety of proteins from their nascent polypeptides. In fact rather than inhibiting G protein pathways, phosducin-like protein 1 (PhLP1) has been shown to be essential for G protein signaling by catalyzing the folding and assembly of the Gbetagamma dimer. PhLP2 and PhLP3 have no role in G protein signaling, but they appear to assist in the folding of proteins essential in regulating cell cycle progression as well as actin and tubulin. Phosducin itself is the only family member that does not participate with CCT in protein folding, but it is believed to have a specific role in visual signal transduction to chaperone Gbetagamma subunits as they translocate to and from the outer and inner segments of photoreceptor cells during light-adaptation.
最初有人提出,磷光蛋白基因家族的成员可作为G蛋白信号的下调因子,通过结合G蛋白βγ二聚体(Gβγ)并抑制其与G蛋白α亚基(Gα)及效应器相互作用的能力来发挥作用。然而,最近的研究结果推翻了这一假说,研究表明磷光蛋白家族的大多数成员可作为伴侣蛋白,与胞质伴侣蛋白复合体(CCT)共同协助多种新生多肽折叠成蛋白质。事实上,磷光蛋白样蛋白1(PhLP1)并非抑制G蛋白信号通路,而是通过催化Gβγ二聚体的折叠和组装,对G蛋白信号传导至关重要。PhLP2和PhLP3在G蛋白信号传导中不起作用,但它们似乎有助于折叠在调节细胞周期进程以及肌动蛋白和微管蛋白方面至关重要的蛋白质。磷光蛋白本身是该家族中唯一不参与CCT介导的蛋白质折叠的成员,但据信它在视觉信号转导中具有特定作用,即在光适应过程中,当Gβγ亚基在光感受器细胞的外段和内段之间转运时,它可作为伴侣蛋白发挥作用。