Phosphatidylinositol 4,5-bisphosphate

Phosphatidylinositol 4,5-bisphosphate or PtdIns(4,5)P₂, also known simply as PIP₂, is a minor phospholipid

Phospholipid

Phospholipids are a class of lipids that are a major component of all cell membranes as they can form lipid bilayers. Most phospholipids contain a diglyceride, a phosphate group, and a simple organic molecule such as choline; one exception to this rule is sphingomyelin, which is derived from...

 component of cell membranes. PtdIns(4,5)P₂ is enriched at the plasma membrane where it is a substrate for a number of important signaling proteins.

PtdIns(4,5)P₂ is formed primarily by the type I phosphatidylinositol 4 phosphate 5 kinases from PI(4)P.

The fatty acid

Fatty acid

In chemistry, especially biochemistry, a fatty acid is a carboxylic acid with a long unbranched aliphatic tail , which is either saturated or unsaturated. Most naturally occurring fatty acids have a chain of an even number of carbon atoms, from 4 to 28. Fatty acids are usually derived from...

s of PIP₂ are variable in different species and tissues, but studies show the most common fatty acids are stearic

Stearic acid

Stearic acid is the saturated fatty acid with an 18 carbon chain and has the IUPAC name octadecanoic acid. It is a waxy solid, and its chemical formula is CH316CO2H. Its name comes from the Greek word στέαρ "stéatos", which means tallow. The salts and esters of stearic acid are called stearates...

 in position 1 and arachidonic in 2.

IP3/DAG pathway

PtdIns(4,5)P₂ functions as an intermediate in the IP3/DAG pathway, which is initiated by ligands binding to G protein-coupled receptors activating the G_q alpha subunit

Gq alpha subunit

Gq protein or Gq/11 is a heterotrimeric G protein subunit that activates phospholipase C . PLC in turn hydrolyzes Phosphatidylinositol 4,5-bisphosphate to diacyl glycerol and inositol triphosphate signal transduction pathway...

. PtdIns(4,5)P₂ is a substrate for hydrolysis by phospholipase C

Phospholipase C

Phosphoinositide phospholipase C is a family of eukaryotic intracellular enzymes that play an important role in signal transduction processes. In general, this enzyme is denoted as Phospholipase C, although three other families of phospholipase C enzymes have been identified in bacteria and in...

 (PLC), a membrane-bound enzyme

Enzyme

Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

 activated through protein receptors such as α1 adrenergic receptors. The products of this reaction are inositol 1,4,5-triphosphate (InsP₃; IP3) and diacylglycerol

Diglyceride

A diglyceride, or a diacylglycerol , is a glyceride consisting of two fatty acid chains covalently bonded to a glycerol molecule through ester linkages....

 (DAG), both of which function as second messengers

Second messenger system

Second messengers are molecules that relay signals from receptors on the cell surface to target molecules inside the cell, in the cytoplasm or nucleus. They relay the signals of hormones like epinephrine , growth factors, and others, and cause some kind of change in the activity of the cell...

. In this cascade, DAG remains on the cell membrane and activates the signal cascade by activating protein kinase C

Protein kinase C

Protein kinase C also known as PKC is a family of enzymes that are involved in controlling the function of other proteins through the phosphorylation of hydroxyl groups of serine and threonine amino acid residues on these proteins. PKC enzymes in turn are activated by signals such as increases in...

 (PKC). PKC in turn activates other cytosolic proteins by phosphorylating them. The effect of PKC could be reversed by phosphatases. IP3 enters the cytoplasm and activates IP3 receptors on the smooth endoplasmic reticulum

Endoplasmic reticulum

The endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...

 (ER), which opens calcium channels on the smooth ER, allowing mobilization of calcium ions through specific Ca²⁺ channels into the cytosol. Calcium participates in the cascade by activating other proteins.

Docking phospholipids

Class I PI 3-kinases

Class I PI 3-kinases

Class I PI 3-kinases are a subgroup of the enzyme family, phosphoinositide 3-kinase that possess a common protein domain structure, substrate specificity, and method of activation...

 phosphorylate PtdIns(4,5)P₂ forming phosphatidylinositol (3,4,5)-trisphosphate

Phosphatidylinositol (3,4,5)-trisphosphate

Phosphatidylinositol -triphosphate , abbreviated PIP3, is the product of the class I phosphoinositide 3-kinases phosphorylation on phosphatidylinositol -bisphosphate .-Discovery:...

 (PtdIns(3,4,5)P₃). Both PtdIns(3,4,5)P₃ and PtdIns(4,5)P₂ not only act as substrates for enzymes but also serve as docking phospholipids that bind specific domains that promote the recruitment of proteins to the plasma membrane and subsequent activation of signaling cascades.

• Examples of proteins activated by PtdIns(3,4,5)P₃ are AKT
  AKT
  Akt, also known as Protein Kinase B , is a serine/threonine protein kinase that plays a key role in multiple cellular processes such as glucose metabolism, cell proliferation, apoptosis, transcription and cell migration.-Family members:...
  
  , PDPK1, Btk
  Bruton's tyrosine kinase
  Bruton's tyrosine kinase is a type of kinase enzyme implicated in the primary immunodeficiency disease X-linked agammaglobulinemia . Its exact mechanism of action remains unknown, but it plays a crucial role in B cell maturation as well as mast cell activation through the high-affinity IgE receptor...
  
  1.
• One mechanism for direct effect of PtdIns(4,5)P₂ is opening of Na⁺ channels as a minor function in growth hormone release by growth hormone-releasing hormone.