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. 2020 Feb 7;8:63. doi: 10.3389/fcell.2020.00063

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Copyright © 2020 Blunsom and Cockcroft.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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The PI(4,5)P₂ cycle. The PI(4,5)P₂ cycle begins with the hydrolysis of PI(4,5)P₂ and formation of the second messengers, I(1,4,5)P₃ and DAG. I(1,4,5)P₃ causes an increase in intracellular calcium concentration before being dephosphorylated into inositol. DAG is phosphorylated to PA at the plasma membrane (PM) by DAG kinase (DAGK) and transferred to the ER via Class IIa PITPs (PI/PA transfer proteins) PITPNM1/2. At the ER, PA, and CTP are converted to CDP-DAG by CDS enzymes (CDS1 and CDS2). CDP-DAG is synthesized into PI and this is catalyzed by the enzyme PI synthase (PIS). PI is transferred to the PM by Class I PITPs (PI/PC transfer proteins) PITPα/β and Class IIa PITPNM1/2, for phosphorylation to PI(4,5)P₂ by the resident enzymes, PI4KIIIα and PIP5K. PITPNM1/2 are also known as Nir2/Nir3.