Phosphorylation and inactivation of BAD by mitochondria-anchored protein kinase A
Phosphorylation and inactivation of BAD by mitochondria-anchored protein kinase A
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DOI：
10.1016/s1097-2765(00)80469-4
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发表时间：
1999-04-01
期刊：
影响因子：
16
通讯作者：
Korsmeyer, SJ
中科院分区：
文献类型：
--
作者：
Harada, H;Becknell, B;Korsmeyer, SJ
细胞表面受体与BCL-2蛋白家族之间的信号通路调控细胞死亡。生存因子诱导BAD的磷酸化和失活，这是一个促凋亡的成员。BAD激酶的纯化(s)鉴定了基于膜的camp依赖性蛋白激酶（PKA）是BAD Ser-112 （S112）位点特异性激酶。pka特异性抑制剂阻断了il -3诱导的内源性BAD的S112磷酸化以及基于线粒体的BAD S112激酶活性。阻断肽破坏II型PKA全酶与A-激酶锚定蛋白（AKAPs）的关联，也抑制BAD磷酸化并消除线粒体中的BAD S112激酶活性。因此，PKA锚定在线粒体上代表了一种集中的亚细胞激酶/底物相互作用，该相互作用在其靶细胞器上失活BAD，以响应生存因子。
Signaling pathways between cell surface receptors and the BCL-2 family of proteins regulate cell death. Survival factors induce the phosphorylation and inactivation of BAD, a proapoptotic member. Purification of BAD kinase(s) identified membrane-based cAMP-dependent protein kinase (PKA) as a BAD Ser-112 (S112) site-specific kinase. PKA-specific inhibitors blocked the IL-3-induced phosphorylation on S112 of endogenous BAD as well as mitochondria-based BAD S112 kinase activity. A blocking peptide that disrupts type II PKA holoenzyme association with A-kinase-anchoring proteins (AKAPs) also inhibited BAD phosphorylation and eliminated the BAD S112 kinase activity at mitochondria. Thus, the anchoring of PKA to mitochondria represents a focused subcellular kinase/substrate interaction that inactivates BAD at its target organelle in response to a survival factor.