Liu Yan-Yun, Brent Gregory A
Department of Medicine, David Geffen School of Medicine at UCLA and VA Greater Los Angles Healthcare System, Los Angeles, CA, USA.
Department of Physiology, David Geffen School of Medicine at UCLA and VA Greater Los Angles Healthcare System, Los Angeles, CA, USA.
Methods Mol Biol. 2018;1801:39-46. doi: 10.1007/978-1-4939-7902-8_5.
TR phosphorylation promotes TR binding to DNA and heterodimerization with RXR. TRβ phosphorylation is induced by thyroid hormone on the cell membrane and phosphorylation by extracellular signal-regulated kinases (ERK), presumably at serine 142. TRα1 N-termini harbors two phosphorylation sites at serine 12 and serine 28/29. Serine 12 is phosphorylated by casein 2 and serine 28/29 by protein kinase A. Mutation analysis of TRα2 identified 2 serine sites, S472 and S473, as the substrates for casein kinase II. Phosphorylated TRα2 does not bind to DNA and dephosphorylated TRα binds to DNA and antagonizes TRα1 binding. Phosphorylation of TR is critical for TR function and T3 signaling and approaches to detection and analysis of phosphorylated TR are described.
甲状腺激素受体（TR）磷酸化促进TR与DNA结合以及与视黄酸X受体（RXR）形成异源二聚体。TRβ磷酸化由甲状腺激素在细胞膜上诱导产生，并由细胞外信号调节激酶（ERK）磷酸化，推测发生在丝氨酸142位点。TRα1的N端在丝氨酸12和丝氨酸28/29处有两个磷酸化位点。丝氨酸12由酪蛋白2磷酸化，丝氨酸28/29由蛋白激酶A磷酸化。TRα2的突变分析确定了2个丝氨酸位点，即S472和S473，为酪蛋白激酶II的底物。磷酸化的TRα2不与DNA结合，而去磷酸化的TR与DNA结合并拮抗TRα1的结合。TR的磷酸化对TR功能和T3信号传导至关重要，本文还描述了检测和分析磷酸化TR的方法。
