Protein kinase C isoforms differentially phosphorylate Ca(v)1.2 alpha(1c).
Protein kinase C isoforms differentially phosphorylate Ca(v)1.2 alpha(1c).
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DOI：
10.1021/bi900322a
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发表时间：
2009-07-21
期刊：
影响因子：
2.9
通讯作者：
Marx, Steven O.
中科院分区：
文献类型：
--
作者：
Yang, Lin;Doshi, Darshan;Morrow, John;Katchman, Alexander;Chen, Xiang;Marx, Steven O.
The regulation of Ca2+ influx through the phosphorylation of the L-type Ca2+ channel, Cav1.2, is important for the modulation of excitation-contraction (E-C) coupling in the heart. Cav1.2 is thought to be the target of multiple kinases that mediate the signals of both the renin-angiotensin and sympathetic nervous systems. Detailed biochemical information regarding the protein phosphorylation reactions involved in the regulation of Cav1.2 is limited. The PKC family of kinases can modulate cardiac contractility in a complex manner, such that contractility is either enhanced or depressed, and relaxation is either accelerated or slowed. We have previously reported that Ser1928 in the C-terminus of α1c was a target for PKCα, ζ and ε phosphorylation. Here, we report the identification of seven PKC phosphorylation sites within the α1c subunit. Using phospho-epitope specific antibodies to Ser1674 and Ser1928, we demonstrate that both sites within C-terminus are phosphorylated in HEK cells in response to PMA. Phosphorylation was inhibited with a PKC inhibitor, bisindolylmaleimide. In Langendorff-perfused rat hearts, both Ser1674 and Ser1928 were phosphorylated in response to PMA. Phosphorylation of Ser1674, but not Ser1928, is PKC isoform-specific, as only PKC α, βI, βII, υ, δ and Θ, but not PKC ε, ζ and η, were able to phosphorylate this site. Our results identify a molecular mechanism by which PKC isoforms can have different effects on channel activity by phosphorylating different residues.
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CAMKII将Ca2+通道的camkii tethers建立，建立了Ca2+信号的本地和专用集成商进行便利。
影响因子：
7.8
作者：
Hudmon, A;Schulman, H;Kim, J;Maltez, JM;Tsien, RW;Pitt, GS
通讯作者：
Pitt, GS
影响因子：
5.5
作者：
He, JQ;Pi, YQ;Kamp, TJ
通讯作者：
Kamp, TJ
影响因子：
64.8
作者：
LACERDA, AE;RAMPE, D;BROWN, AM
通讯作者：
BROWN, AM
DOI：
10.1073/pnas.210384297
发表时间：
2000-10-24
影响因子：
11.1
作者：
McHugh, D;Sharp, EM;Catterall, WA
通讯作者：
Catterall, WA
DOI：
10.1073/pnas.96.11.6400
发表时间：
1999-05-25
影响因子：
11.1
作者：
Dorn, GW;Tepe, NM;Liggett, SB
通讯作者：
Liggett, SB