Kato Satomi, Ding Jixin, Du Keyong
Molecular Oncology Research Institute, Tufts-New England Medical Center, Boston, MA 02111, USA.
Biochem Biophys Res Commun. 2007 Mar 23;354(4):1061-6. doi: 10.1016/j.bbrc.2007.01.094. Epub 2007 Jan 25.
Members of Akt family are highly conserved protein kinase and yet, they show clearly distinct in vivo functions. Here, we have examined the abilities of Akt1 and Akt2 to activate CREB. We found that, in contrast to Akt1 that induces CREB phosphorylation at Ser-133 and CREB target gene expression, Akt2 was unable to induce CREB phosphorylation at Ser-133 in vivo and CREB target gene expression. This difference is specific to CREB as both Akt1 and Akt2 similarly inhibits FoxO1 mediated gene expression. We further showed that the regulatory domain of Akt plays a critical role to confer Akt substrate specificity as substitution of regulatory domain of Akt1 with that of Akt2 abolished the ability of Akt1 to activate CREB. We suggest that the regulatory domain of Akts contributes to the functional difference between Akt1 and Akt2.
Akt家族成员是高度保守的蛋白激酶，然而，它们在体内表现出明显不同的功能。在此，我们研究了Akt1和Akt2激活CREB的能力。我们发现，与诱导Ser-133处CREB磷酸化及CREB靶基因表达的Akt1相反，Akt2在体内无法诱导Ser-133处CREB磷酸化及CREB靶基因表达。这种差异对CREB具有特异性，因为Akt1和Akt2同样抑制FoxO1介导的基因表达。我们进一步表明，Akt的调节结构域在赋予Akt底物特异性方面起关键作用，因为用Akt2的调节结构域替换Akt1的调节结构域消除了Akt1激活CREB的能力。我们认为Akts的调节结构域导致了Akt1和Akt2之间的功能差异。
