整合素连接激酶和环核苷酸依赖性蛋白激酶对1型蛋白磷酸酶抑制蛋白的磷酸化作用。

Phosphorylation of protein phosphatase type-1 inhibitory proteins by integrin-linked kinase and cyclic nucleotide-dependent protein kinases.

作者信息

Erdodi Ferenc, Kiss Eniko, Walsh Michael P, Stefansson Bjarki, Deng Jing Ti, Eto Masumi, Brautigan David L, Hartshorne David J

机构信息

Department of Medical Chemistry, Medical and Health Science Center, University of Debrecen, H-4012 Debrecen, 18/B, Bem tér, Hungary.

出版信息

Biochem Biophys Res Commun. 2003 Jun 27;306(2):382-7. doi: 10.1016/s0006-291x(03)00976-8.

DOI:10.1016/s0006-291x(03)00976-8

PMID:12804574

Abstract

Protein phosphatases play key roles in cellular regulation and are subjected to control by protein inhibitors whose activity is in turn regulated by phosphorylation. Here we investigated the possible regulation of phosphorylation-dependent type-1 protein phosphatase (PP1) inhibitors, CPI-17, PHI-1, and KEPI, by various kinases. Protein kinases A (PKA) and G (PKG) phosphorylated CPI-17 at the inhibitory site (T38), but not PHI-1 (T57). Phosphorylated CPI-17 inhibited the activity of both the PP1 catalytic subunit (PP1c) and the myosin phosphatase holoenzyme (MPH) with IC(50) values of 1-8 nM. PKA predominantly phosphorylated a site distinct from the inhibitory T73 in KEPI, whereas PKG was ineffective. Integrin-linked kinase phosphorylated KEPI (T73) and this dramatically increased inhibition of PP1c (IC(50)=0.1 nM) and MPH (IC(50)=8 nM). These results suggest that the regulatory phosphorylation of CPI-17 and KEPI may involve distinct kinases and signaling pathways.

摘要

蛋白磷酸酶在细胞调节中发挥关键作用，并受到蛋白抑制剂的调控，而蛋白抑制剂的活性又受磷酸化作用的调节。在此，我们研究了各种激酶对磷酸化依赖性1型蛋白磷酸酶（PP1）抑制剂CPI-17、PHI-1和KEPI的潜在调节作用。蛋白激酶A（PKA）和G（PKG）在抑制位点（T38）使CPI-17磷酸化，但未使PHI-1（T57）磷酸化。磷酸化的CPI-17抑制PP1催化亚基（PP1c）和肌球蛋白磷酸酶全酶（MPH）的活性，IC（50）值为1 - 8 nM。PKA主要使KEPI中与抑制性T73不同的位点磷酸化，而PKG则无此作用。整合素连接激酶使KEPI（T73）磷酸化，这显著增强了对PP1c（IC（50）=0.1 nM）和MPH（IC（50）=8 nM）的抑制作用。这些结果表明，CPI-17和KEPI的调节性磷酸化可能涉及不同的激酶和信号通路。