Biomaterial Database

Activation of protein kinase C by phosphatidylinositol 4,5-bisphosphate: possible involvement in Na+/H+ antiport down-regulation and cell proliferation. 1991

A Chauhan, and V P Chauhan, and H Brockerhoff

Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314.

Phosphatidylinositol 4,5-bisphosphate (PIP2) as well as diacylglycerol (DG) activate protein kinase C (PKC) in the presence of calcium and phosphatidylserine. The pH at half-activation (pK) is 6.2 for DG.PKC and 7.7 for PIP2.PKC. Since the second monophosphate proton in position 5 of the PIP2 inositol (i.e., the last ionizable proton) has a pK of 7.7 (Van Paridon et al., (1986) Biochim. Biophys. Acta. 877, 216), the active effector is a fully deprotonated PIP2. Activation of PKC by PIP2 thus may follow intracellular alkalinization and be tied to the down-regulation of the Na+/H+ antiport mechanism. Since alkalinization is obligatory for cell proliferation, PIP2(5-).Ca.PKC may also be the gate that opens the pathways toward this and connected cellular reactions. A PIP2 analog in which inositol carbons 2-4 and the 4-phosphate have been removed, 1-phosphatidyl-rac-glycerol-3-phosphate (PGP), is completely inactive as PKC effector; this suggests that both 4-and 5-phosphate are engaged in the PIP2(5-).Ca.PKC complex. A model of the activated kinase takes this into account.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008954	Models, Biological	Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.	Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D010716	Phosphatidylinositols	Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to the hexahydroxy alcohol, myo-inositol. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid, myo-inositol, and 2 moles of fatty acids.	Inositide Phospholipid,Inositol Phosphoglyceride,Inositol Phosphoglycerides,Inositol Phospholipid,Phosphoinositide,Phosphoinositides,PtdIns,Inositide Phospholipids,Inositol Phospholipids,Phosphatidyl Inositol,Phosphatidylinositol,Inositol, Phosphatidyl,Phosphoglyceride, Inositol,Phosphoglycerides, Inositol,Phospholipid, Inositide,Phospholipid, Inositol,Phospholipids, Inositide,Phospholipids, Inositol
D011493	Protein Kinase C	An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.	Calcium Phospholipid-Dependent Protein Kinase,Calcium-Activated Phospholipid-Dependent Kinase,PKC Serine-Threonine Kinase,Phospholipid-Sensitive Calcium-Dependent Protein Kinase,Protein Kinase M,Calcium Activated Phospholipid Dependent Kinase,Calcium Phospholipid Dependent Protein Kinase,PKC Serine Threonine Kinase,Phospholipid Sensitive Calcium Dependent Protein Kinase,Phospholipid-Dependent Kinase, Calcium-Activated,Serine-Threonine Kinase, PKC
D001921	Brain	The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.	Encephalon
D002352	Carrier Proteins	Proteins that bind or transport specific substances in the blood, within the cell, or across cell membranes.	Binding Proteins,Carrier Protein,Transport Protein,Transport Proteins,Binding Protein,Protein, Carrier,Proteins, Carrier
D004789	Enzyme Activation	Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.	Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D006706	Homeostasis	The processes whereby the internal environment of an organism tends to remain balanced and stable.	Autoregulation
D006863	Hydrogen-Ion Concentration	The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH	pH,Concentration, Hydrogen-Ion,Concentrations, Hydrogen-Ion,Hydrogen Ion Concentration,Hydrogen-Ion Concentrations
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia