CALCINEURIN ASSOCIATED WITH THE INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR-FKBP12 COMPLEX MODULATES CA2+ FLUX
CALCINEURIN ASSOCIATED WITH THE INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR-FKBP12 COMPLEX MODULATES CA2+ FLUX
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DOI：
10.1016/0092-8674(95)90124-8
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发表时间：
1995-11-03
期刊：
影响因子：
64.5
通讯作者：
SNYDER, SH
中科院分区：
文献类型：
--
作者：
CAMERON, AM;STEINER, JP;SNYDER, SH
免疫抑制药物FK506与免疫亲和素蛋白FKBP12结合，并抑制其Pro-异构酶活性。然而，免疫抑制作用是通过FK506-FKBP12抑制钙激活的磷酸酶钙调神经磷酸酶来实现的。FKBP12的细胞生理学作用尚不清楚。在没有FK506的情况下，FKBP12与RyR和IP(3)R钙离子通道有物理上的联系，加入FK506破坏了这些复合体，FKBP12的解离导致了这两种情况下通道钙电导的改变。我们现在报道，钙调神经磷酸酶与IP(3)R-FKBP12和RyR-FKBP12受体复合体在生理上相关，这种相互作用可以被FK506或雷帕霉素破坏，通过FKBP12锚定在IP(3)R上的钙调神经磷酸酶调节受体的磷酸化状态，导致对IP3介导的钙离子通量的动态钙敏感调节。
The immunosuppressant drug FK506 binds to the immunophilin protein FKBP12 and inhibits its prolyl isomerase activity. Immunosuppresive actions, however, are mediated via an FK506-FKBP12 inhibition of the Ca2+-activated phosphatase calcineurin. Physiologic cellular roles for FKBP12 have remained unclear. FKBP12 is physically associated with the RyR and IP(3)R Ca2+ channels in the absence of FK506, with added FK506 disrupting these complexes, Dissociation of FKBP12 results in alteration of channel Ca2+ conductance in both cases. We now report that calcineurin is physiologically associated with the IP(3)R-FKBP12 and RyR-FKBP12 receptor complexes and that this interaction can be disrupted by FK506 or rapamycin, Calcineurin anchored to the IP(3)R via FKBP12 regulates the phosphorylation status of the receptor, resulting in a dynamic Ca2+-sensitive regulation of IP3-mediated Ca2+ flux.