Phosphatidylinositol 4,5-bisphosphate decreases the concentration of Ca2+, phosphatidylserine and diacylglycerol required for protein kinase C α to reach maximum activity.

The C2 domain of PKCα possesses two different binding sites, one for Ca(2+) and phosphatidylserine and a second one that binds PIP2 with very high affinity. The enzymatic activity of PKCα was studied by activating it with large unilamellar lipid vesicles, varying the concentration of Ca(2+) and the...

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Autores principales:	Antonio L Egea-Jiménez, Angel Pérez-Lara, Senena Corbalán-García, Juan C Gómez-Fernández
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/90d11193c24047289f7b2ed2815804d2
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spelling	oai:doaj.org-article:90d11193c24047289f7b2ed2815804d22021-11-18T07:37:53ZPhosphatidylinositol 4,5-bisphosphate decreases the concentration of Ca2+, phosphatidylserine and diacylglycerol required for protein kinase C α to reach maximum activity.1932-620310.1371/journal.pone.0069041https://doaj.org/article/90d11193c24047289f7b2ed2815804d22013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23874859/?tool=EBIhttps://doaj.org/toc/1932-6203The C2 domain of PKCα possesses two different binding sites, one for Ca(2+) and phosphatidylserine and a second one that binds PIP2 with very high affinity. The enzymatic activity of PKCα was studied by activating it with large unilamellar lipid vesicles, varying the concentration of Ca(2+) and the contents of dioleylglycerol (DOG), phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphadidylserine (POPS) in these model membranes. The results showed that PIP2 increased the Vmax of PKCα and, when the PIP2 concentration was 5 mol% of the total lipid in the membrane, the addition of 2 mol% of DOG did not increase the activity. In addition PIP2 decreases K0.5 of Ca(2+) more than 3-fold, that of DOG almost 5-fold and that of POPS by a half. The K0.5 values of PIP2 amounted to only 0.11 µM in the presence of DOG and 0.39 in its absence, which is within the expected physiological range for the inner monolayer of a mammalian plasma membrane. As a consequence, PKCα may be expected to operate near its maximum capacity even in the absence of a cell signal producing diacylglycerol. Nevertheless, we have shown that the presence of DOG may also help, since the K0.5 for PIP2 notably decreases in its presence. Taken together, these results underline the great importance of PIP2 in the activation of PKCα and demonstrate that in its presence, the most important cell signal for triggering the activity of this enzyme is the increase in the concentration of cytoplasmic Ca(2+).Antonio L Egea-JiménezAngel Pérez-LaraSenena Corbalán-GarcíaJuan C Gómez-FernándezPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 7, p e69041 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Antonio L Egea-Jiménez Angel Pérez-Lara Senena Corbalán-García Juan C Gómez-Fernández Phosphatidylinositol 4,5-bisphosphate decreases the concentration of Ca2+, phosphatidylserine and diacylglycerol required for protein kinase C α to reach maximum activity.
description	The C2 domain of PKCα possesses two different binding sites, one for Ca(2+) and phosphatidylserine and a second one that binds PIP2 with very high affinity. The enzymatic activity of PKCα was studied by activating it with large unilamellar lipid vesicles, varying the concentration of Ca(2+) and the contents of dioleylglycerol (DOG), phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphadidylserine (POPS) in these model membranes. The results showed that PIP2 increased the Vmax of PKCα and, when the PIP2 concentration was 5 mol% of the total lipid in the membrane, the addition of 2 mol% of DOG did not increase the activity. In addition PIP2 decreases K0.5 of Ca(2+) more than 3-fold, that of DOG almost 5-fold and that of POPS by a half. The K0.5 values of PIP2 amounted to only 0.11 µM in the presence of DOG and 0.39 in its absence, which is within the expected physiological range for the inner monolayer of a mammalian plasma membrane. As a consequence, PKCα may be expected to operate near its maximum capacity even in the absence of a cell signal producing diacylglycerol. Nevertheless, we have shown that the presence of DOG may also help, since the K0.5 for PIP2 notably decreases in its presence. Taken together, these results underline the great importance of PIP2 in the activation of PKCα and demonstrate that in its presence, the most important cell signal for triggering the activity of this enzyme is the increase in the concentration of cytoplasmic Ca(2+).
format	article
author	Antonio L Egea-Jiménez Angel Pérez-Lara Senena Corbalán-García Juan C Gómez-Fernández
author_facet	Antonio L Egea-Jiménez Angel Pérez-Lara Senena Corbalán-García Juan C Gómez-Fernández
author_sort	Antonio L Egea-Jiménez
title	Phosphatidylinositol 4,5-bisphosphate decreases the concentration of Ca2+, phosphatidylserine and diacylglycerol required for protein kinase C α to reach maximum activity.
title_short	Phosphatidylinositol 4,5-bisphosphate decreases the concentration of Ca2+, phosphatidylserine and diacylglycerol required for protein kinase C α to reach maximum activity.
title_full	Phosphatidylinositol 4,5-bisphosphate decreases the concentration of Ca2+, phosphatidylserine and diacylglycerol required for protein kinase C α to reach maximum activity.
title_fullStr	Phosphatidylinositol 4,5-bisphosphate decreases the concentration of Ca2+, phosphatidylserine and diacylglycerol required for protein kinase C α to reach maximum activity.
title_full_unstemmed	Phosphatidylinositol 4,5-bisphosphate decreases the concentration of Ca2+, phosphatidylserine and diacylglycerol required for protein kinase C α to reach maximum activity.
title_sort	phosphatidylinositol 4,5-bisphosphate decreases the concentration of ca2+, phosphatidylserine and diacylglycerol required for protein kinase c α to reach maximum activity.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/90d11193c24047289f7b2ed2815804d2
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Phosphatidylinositol 4,5-bisphosphate decreases the concentration of Ca2+, phosphatidylserine and diacylglycerol required for protein kinase C α to reach maximum activity.

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