Activation of protein kinase B β and γ isoforms by insulin in vivo and by 3-phosphoinositide-dependent protein kinase-1 in vitro:: comparison with protein kinase B α
Activation of protein kinase B β and γ isoforms by insulin in vivo and by 3-phosphoinositide-dependent protein kinase-1 in vitro:: comparison with protein kinase B α
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DOI：
10.1042/bj3310299
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发表时间：
1998-04-01
影响因子：
4.1
通讯作者：
Alessi, DR
中科院分区：
文献类型：
--
作者：
Walker, KS;Deak, M;Alessi, DR
蛋白激酶B（PKB）的三种哺乳动物亚型的调节和催化特性进行了比较。所有三种亚型（PKB α，PKB β和PKB γ）以相似的速率磷酸化，并通过3-磷酸肌醇依赖性蛋白激酶-1（PDK 1）激活至相似的程度。每种酶的磷酸化和活化都需要PtdIns（3，4，5）P-3或PtdIns（3，4）P-2以及PDK 1的存在。PDK 1激活PKB β和PKB γ时，伴随着相当于PKB α中Thr（308）残基的磷酸化，即Thr（309）（PKB β）和Thr（305）（PKB γ）。经PDK 1激活的PKB γ对一系列肽具有与PKB α和PKB β相同的底物特异性。在293细胞中，胰岛素样生长因子-1可激活PKB γ并使其在Thr（305）处磷酸化。用胰岛素刺激大鼠脂肪细胞或大鼠肝细胞以相似的动力学诱导PKB α和PKB β的活化。在脂肪细胞刺激后，PKB β的活性是PKB α的两倍，但在肝细胞中，PKB α的活性是PKB β的四倍。胰岛素在体内诱导大鼠骨骼肌中PKB α的活化，而PKB β的活化很少。胰岛素不诱导脂肪细胞、肝细胞或骨骼肌中的PKB γ活性，但PKB γ是大鼠L 6肌管（一种骨骼肌细胞系）中胰岛素激活的主要亚型。
The regulatory and catalytic properties of the three mammalian isoforms of protein kinase B (PKB) have been compared. All three isoforms (PKB alpha, PKB beta and PKB gamma) were phosphorylated at similar rates and activated to similar extents by 3-phosphoinositide-dependent protein kinase-1 (PDK1). Phosphorylation and activation of each enzyme required the presence of PtdIns(3,4,5)P-3 or PtdIns(3,4)P-2, as well as PDK1. The activation of PKB beta and PKB gamma by PDK1 was accompanied by the phosphorylation of the residues equivalent to Thr(308) in PKB alpha, namely Thr(309) (PKB beta) and Thr(305) (PKB gamma). PKB gamma which had been activated by PDK1 possessed a substrate specificity identical with that of PKB alpha and PKB beta towards a range of peptides, The activation of PKB gamma and its phosphorylation at Thr(305) was triggered by insulin-like growth factor-1 in 293 cells. Stimulation of rat adipocytes or rat hepatocytes with insulin induced the activation of PKB alpha and PKB beta with similar kinetics. After stimulation of adipocytes, the activity of PKB beta was twice that of PKB alpha, but in hepatocytes PKB alpha activity was four-fold higher than PKB beta. Insulin induced the activation of PKB alpha in rat skeletal muscle in vivo, with little activation of PKB beta. Insulin did not induce PKB gamma activity in adipocytes, hepatocytes or skeletal muscle, but PKB gamma was the major isoform activated by insulin in rat L6 myotubes (a skeletal-muscle cell line).