PIP2 phosphatidylinositol transduction

When attention is directed toward the phospholipase.C found in mammalian tissue, a rather unique and different substrate profile is evident. It appears that the most favored substrate status must be assigned to the inositol- containing phosphoglycerides, namely, phosphatidylinositol (PI), phosphatidylinositol phosphate (PIP), and phosphatidylinositol-4,5-bisphosphate (PIP2). There is some evidence that the plasma membrane of certain mammalian cells contains a phospholipase C with high specificity for the bisphosphate, PIP2. The latter enzymatic interaction would be closely associated with the signal transduction pathway in mammalian cells. 

The transduction of many hormonal and neuronal signals occurs through receptor-mediated activation of phosphoinositidase C (phospholipase C). This enzyme hydrolyzes phosphatidylinositol 4,5-bis-(phosphate) (PIP2) into 1,2-diacylglycerol and n-inositol 1,4,5-tris-(phosphate) in the plasma membrane. Both products are second messengers that, respectively, stimulate protein kinase C and release calcium from intracellular stores located in the endoplasmic reticulum (100). D-Inositol l,4,5-tris(phosphate) is converted via intermediary compounds to myoinositol. In return this is converted to phosphatidylinositol, which is used to replenish PIP2. 

Phosphatidylinositol bisphosphate (PIP2) Belongs to the category of anionic lipids and is involved in signal transduction as a classical Kpid second messenger. 

Autophosphorylation of the insulin receptor leads to phosphorylation of insulin receptor substrate (IRS). IRS comes in four different forms (IRS-1, IRS-2, IRS-3 and IRS-4). In muscle tissue, IRS-1 is the most important form for mediating insulin-signal transduction and lRS-1 impairment has been observed in muscle tissue of humans with DM-2 (Glund and Zierath, 2005). lRS-1 has many tyrosine phosphorylation sites. When these sites are phosphorylated by the insulin receptor, multiple insulin signals are enabled (Sun et al., 1993). IRS-1 also has several serine phosphorylation sites phosphorylation of serine residue 1101 results in inhibition of insulin signalling and provides a possible mechanism for IR (Li et al., 2004). After IRS is phosphorylated, it recruits and activates phosphatidylinositol 3-kinase (PI3-kinase). PI3-kinase phosphorylates phosphatidylinositol-4,5-bisphosphate (PIP2) to... 

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