Blitzer R D, Connor J H, Brown G P, Wong T, Shenolikar S, Iyengar R, Landau E M
Bronx VA Medical Center and Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029, USA.
Science. 1998 Jun 19;280(5371):1940-2. doi: 10.1126/science.280.5371.1940.
Long-term potentiation (LTP) at the Schaffer collateral-CA1 synapse involves interacting signaling components, including calcium (Ca2+)/calmodulin-dependent protein kinase II (CaMKII) and cyclic adenosine monophosphate (cAMP) pathways. Postsynaptic injection of thiophosphorylated inhibitor-1 protein, a specific inhibitor of protein phosphatase-1 (PP1), substituted for cAMP pathway activation in LTP. Stimulation that induced LTP triggered cAMP-dependent phosphorylation of endogenous inhibitor-1 and a decrease in PP1 activity. This stimulation also increased phosphorylation of CaMKII at Thr286 and Ca2+-independent CaMKII activity in a cAMP-dependent manner. The blockade of LTP by a CaMKII inhibitor was not overcome by thiophosphorylated inhibitor-1. Thus, the cAMP pathway uses PP1 to gate CaMKII signaling in LTP.
在海马体苔状纤维- CA1突触处的长时程增强（LTP）涉及相互作用的信号传导成分，包括钙（Ca2+）/钙调蛋白依赖性蛋白激酶II（CaMKII）和环磷酸腺苷（cAMP）信号通路。向突触后注射硫代磷酸化抑制因子1蛋白（一种蛋白磷酸酶-1（PP1）的特异性抑制剂），可替代LTP中cAMP信号通路的激活。诱导LTP的刺激引发内源性抑制因子1的cAMP依赖性磷酸化，并导致PP1活性降低。这种刺激还以cAMP依赖性方式增加了CaMKII在苏氨酸286位点的磷酸化以及Ca2+非依赖性CaMKII活性。CaMKII抑制剂对LTP的阻断作用不能被硫代磷酸化抑制因子1克服。因此，cAMP信号通路利用PP1来调控LTP中的CaMKII信号传导。
