Phosphatidylinositol 4.5- bisphosphate

Phosphatidylinositol 4,5-bisphosphate is a derivative of phosphatidylinositol in which the inositol ring is phosphorylated at positions 4 and 5. 

Hormonal factors and other stimuli by activating phospholipase C-(3 or -y isoforms stimulate the breakdown of phosphatidylinositol 4,5-bisphosphate to inositol 1,4,5-trisphosphate and diacylglycerol, a reaction called PI response. 

TLR-2. Evidence for the bridging role of Mai comes from the presence of a phosphatidylinositol 4,5-bisphosphate (PEP2) binding domain at its N-terminus. This domain recruits Mai to areas of the plasma membrane rich in PEP2 and these areas have been shown to contain TLR-4. 

TRPVl, also known as the capsaicin- or vanilloid-receptor, is a nonselective cation channel expressed e.g., in neurons of the dorsal root and trigeminal ganglions, which integrates multiple pain-producing stimuli including heat, protons, capsaicin, and resiniferatoxin. In addition, TRPVl currents can be activated by ananda-mide, protein kinase C (PKC), and by hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2). 

Covalent regulation. Following occupation and activation of the M2 acetyl choline receptors, phospholipase C (PLC), is activated and both inositol (l,4,5)-trisphosphate (IP3), and diacylglycerol (DAG), are formed by hydrolysis of phosphatidylinositol (4,5)-bisphosphate (PIP2). 

Membrane associations can occur by selective protein binding to lipid head groups. One example is spectrin, which binds to phosphatidylinositol-4,5-bisphosphate by means of a pleckstrin-homology (PH) domain [5] (Fig. 2-5). and also to phosphatidyl serine [6] (Fig. 2-6). 

Berstein, G., Blank, J. L., Smrcka, A. V. etal. Reconstitution of agonist stimulated phosphatidylinositol 4-5 bisphosphate hydrolysis using purified mi muscarinic receptor, Gq/11, and phospholipase C-Pl. /. Biol. Chem. 267 8081-8088, 1992. 

FIGURE 14-6 Main signaling pathways for histamine receptors. Histamine can couple to a variety of G-protein-linked signal transduction pathways via its four different receptors. The Hj receptor activates the phosphatidylinositol turnover via Gq/11 proteins. The other receptors either positively (H2 receptor) or negatively (H3 and H4 receptor) regulate adenylyl cyclase activity via Gs and GUo protein activation respectively. Several additional signaling pathways have been described, which are not shown. Abbreviations PfP2, phosphatidylinositol 4,5-bisphosphate PIC, phospholipase C AC, adenylyl cyclase ATP, adenosine triphosphate cAMP, cyclic AMP PKC, protein kinase C PICA, protein kinase A. 

The family of heterotrimeric G proteins is involved in transmembrane signaling in the nervous system, with certain exceptions. The exceptions are instances of synaptic transmission mediated via receptors that contain intrinsic enzymatic activity, such as tyrosine kinase or guanylyl cyclase, or via receptors that form ion channels (see Ch. 10). Heterotrimeric G proteins were first identified, named and characterized by Alfred Gilman, Martin Rodbell and others close to 20 years ago. They consist of three distinct subunits, a, (3 and y. These proteins couple the activation of diverse types of plasmalemma receptor to a variety of intracellular processes. In fact, most types of neurotransmitter and peptide hormone receptor, as well as many cytokine and chemokine receptors, fall into a superfamily of structurally related molecules, termed G-protein-coupled receptors. These receptors are named for the role of G proteins in mediating the varied biological effects of the receptors (see Ch. 10). Consequently, numerous effector proteins are influenced by these heterotrimeric G proteins ion channels adenylyl cyclase phosphodiesterase (PDE) phosphoinositide-specific phospholipase C (PI-PLC), which catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) and phospholipase A2 (PLA2), which catalyzes the hydrolysis of membrane phospholipids to yield arachidonic acid. In addition, these G proteins have been implicated in... 

The Chilton Conference nomenclature for inositol lipids is used throughout this chapter, e.g. PI, PI4P, PI(4,5)P2 for phosphatidylinositol, phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate respectively. Note that the IUB-recommended nomenclature for these lipids is Ptdlns, PtdIns4P and PtdIns(4,5)P2 (see Ch. 3). 

PAM peptidylglycine a-amidating monooxygenase Ptdlns 4,5P2 phosphatidylinositol 4,5-bisphosphate... 

PIP2 phosphatidylinositol 4,5-bisphosphate SAICAR succinylaminoimidazole carboxamide ribotide... 

Figure 6.6. Structure and formation of phosphatidylinositol (Ptdlns), phosphatidylinositol 4-phosphate (PIP) and phosphatidylinositol 4,5-bisphosphate (PIP2). See text for details.

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