کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8474388 | 1550425 | 2015 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Phospholamban pentamers attenuate PKA-dependent phosphorylation of monomers
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
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چکیده انگلیسی
Phospholamban (PLN) is a key regulator of cardiac contraction and relaxation through its inhibition of the sarco/endoplasmic reticulum Ca2Â +-ATPase (SERCA2a). The inhibitory effect is attenuated upon protein kinase A (PKA) dependent phosphorylation of PLN. PLN exists in an equilibrium of pentamers and monomers. While monomers inhibit SERCA2a by direct interaction, the function of the pentamers is still unclear. Here, we tested the hypothesis that the PLN pentamer exhibits an important regulatory role by modifying PKA-dependent phosphorylation of inhibitory monomeric PLN subunits. Using Western blot analyses and antibodies specific for PKA-dependent phosphorylation of PLN, pentamers showed stronger signals than monomers both in transfected HEK293 cells and in cardiomyocytes. Upon activation of PKA, phosphorylation of protomers in the PLN pentamers increased faster and at lower levels of stimulation than PLN monomers, suggesting pentamers as the preferred PKA target. The comparison of phosphorylation patterns at different pentamer/monomer ratios revealed that pentamers delay phosphorylation of PLN monomers. A mechanistic explanation was provided by co-immunoprecipitation that suggested high affinity of PKA for PLN pentamers. Both monomers and pentamers were pulled down with SERCA2a indicating co-localization. Unlike pentamers, phosphorylated PLN monomers fully dissociated from the Ca2Â +-ATPase upon stimulation of PKA. These findings suggest a model where PLN pentamers reduce phosphorylation of monomers at baseline and delay monomer phosphorylation upon PKA stimulation leading to increased interaction of PLN monomers with SERCA2a.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular and Cellular Cardiology - Volume 80, March 2015, Pages 90-97
Journal: Journal of Molecular and Cellular Cardiology - Volume 80, March 2015, Pages 90-97
نویسندگان
Tanja Wittmann, Martin J. Lohse, Joachim P. Schmitt,