Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, BT 110, 3801 University Street, Montreal, Quebec H3A 2B4, Canada.
Neurosci Lett. 2011 Oct 31;504(3):306-10. doi: 10.1016/j.neulet.2011.09.053. Epub 2011 Oct 1.
Novel protein kinase Cs (nPKCs) contain an N-terminal C2 domain that cannot bind to calcium. We have previously shown that the Aplysia novel PKC Apl II's C2 domain inhibits binding of diacylglycerol (DAG) to the C1 domain and that this inhibition is removed by phosphatidic acid (PA) binding to the C1b domain. Another model for C2 domain regulation of nPKCs suggests that the C2 domain binds to receptors for activated C kinase (RACKs) to assist in kinase translocation and activation. In the present study, we examined how a pharmacological peptide derived from RACK-binding site in the vertebrate novel PKCɛ regulates translocation of PKC Apl II from the cytosol to the plasma membrane. We found that a C2 domain-derived inhibitor peptide inhibited PKC Apl II translocation. This inhibition was removed by R273H mutation in the C1b domain and by phosphatidic acid, which can both remove C2-domain mediated inhibition suggesting that the peptide can regulate C1-C2 domain interactions.
新型蛋白激酶 C（nPKC）含有一个不能结合钙的 N 端 C2 结构域。我们之前曾表明，海兔新型 PKC Apl II 的 C2 结构域抑制二酰基甘油（DAG）与 C1 结构域的结合，而这种抑制作用可被 C1b 结构域结合的磷酸脂酰肌醇（PA）所去除。nPKC 的 C2 结构域调节的另一个模型表明，C2 结构域与激活的 C 激酶受体（RACK）结合，以协助激酶易位和激活。在本研究中，我们研究了来自脊椎动物新型 PKCɛ 的 RACK 结合位点的药理学肽如何调节 PKC Apl II 从细胞质向质膜的易位。我们发现，C2 结构域衍生的抑制剂肽抑制了 PKC Apl II 的易位。这种抑制作用可被 C1b 结构域中的 R273H 突变和 PA 去除，PA 也可去除 C2 结构域介导的抑制作用，表明该肽可以调节 C1-C2 结构域相互作用。
