Lai Y, Peterson B Z, Catterall W A
Department of Pharmacology, University of Washington, Seattle 98195.
J Neurochem. 1993 Oct;61(4):1333-9. doi: 10.1111/j.1471-4159.1993.tb13626.x.
Multiple sites on the alpha 1 and beta subunits of purified skeletal muscle calcium channels are phosphorylated by cyclic AMP-dependent protein kinase, resulting in three different tryptic phosphopeptides derived from each subunit. Phosphoprotein phosphatases dephosphorylated these sites selectively. Phosphoprotein phosphatase 1 (PP1) and phosphoprotein phosphatase 2A (PP2A) dephosphorylated both alpha 1 and beta subunits at similar rates, whereas calcineurin dephosphorylated beta subunits preferentially. PP1 dephosphorylated phosphopeptides 1 and 2 of the alpha 1 subunit more rapidly than phosphopeptide 3. In contrast, PP2A dephosphorylated phosphopeptide 3 of the alpha 1 subunit preferentially. All three phosphoprotein phosphatases preferentially dephosphorylated phosphopeptide 1 of the beta subunit and dephosphorylated phosphopeptides 2 and 3 more slowly. Mn2+ increased the rate and extent of dephosphorylation of all sites by calcineurin so that > 80% dephosphorylation of both alpha 1 and beta subunits was obtained. The results demonstrate selective dephosphorylation of different phosphorylation sites on the alpha 1 and beta subunits of skeletal muscle calcium channels by the three principal serine/threonine phosphoprotein phosphatases.
纯化骨骼肌钙通道α1和β亚基上的多个位点被环磷酸腺苷依赖性蛋白激酶磷酸化，每个亚基产生三种不同的胰蛋白酶磷酸肽。磷蛋白磷酸酶选择性地使这些位点去磷酸化。磷蛋白磷酸酶1（PP1）和磷蛋白磷酸酶2A（PP2A）以相似的速率使α1和β亚基去磷酸化，而钙调神经磷酸酶优先使β亚基去磷酸化。PP1使α1亚基的磷酸肽1和2去磷酸化的速度比磷酸肽3快。相反，PP2A优先使α1亚基的磷酸肽3去磷酸化。所有三种磷蛋白磷酸酶都优先使β亚基的磷酸肽1去磷酸化，使磷酸肽2和3去磷酸化的速度较慢。Mn2+增加了钙调神经磷酸酶对所有位点去磷酸化的速率和程度，从而使α1和β亚基的去磷酸化率均超过80%。结果表明，三种主要的丝氨酸/苏氨酸磷蛋白磷酸酶对骨骼肌钙通道α1和β亚基上不同的磷酸化位点进行选择性去磷酸化。
