Phosphoinositide 3-Kinase Review of Classes and Role in Mammals

901 Words 4 Pages
Enzymes play a vital role in biological systems as signaling molecules. Signaling occurs though a chemical reaction that enzymes help catalyze by allowing it to occur through a pathway with lower activation energy (Domin and Waterfield, 1997). Enzymes are made from a chain or chains of amino acids that are linked by peptide bonds, otherwise known as proteins. One particular enzyme pathway of interest is phosphoinositide 3-kinase (P13K). This enzyme is a lipid kinase that has further signaling activity once activated, also known as a cascade induction. P13K cascade mechanism will further be explained below. Phosphoinositide 3-kinase is pleiotropic, meaning this one enzyme has different effects on different cells (Domin and Waterfield, …show more content…
These two further bind to pleckstrin homology (PH) domains which are found in many cytokines. PH selectively and specifically binds to these two PtdIns’ and is the basis of PI3K signaling specificity (Fruman and Cantley, 2002). PI3K signaling can be stopped by dephosphorylating PtdIns(3,4,5)P3 and converting it to PtdIns(3,4)P2 by two major phosphatases known as PTEN, a tumor suppressor, and SHIP (Fruman and Cantley, 2002).
P13K can also be activated by Ras. This activation stimulates a conformational change that inhibits apoptosis as well as residue mutations and T cell adhesion and migration (Pacold et al., 2000).The conformation change suggests that Ras binding could cause an allosteric inhibition (Pacold et al., 2000). Figure 2 shows the enzyme complex compromised of both Ras and PI3Kγ showing the Ras binding domain, a C2, helical and catalytic domains (Pacold et al., 2000). Amongst other techniques used to analyze PI3K, a Western Blot was used to show Class 1B was indeed detected in cells used in these experiments (Pacold et al., 2000).

Figure 2. A- Crystal structure of Ras binding to PI3Kγ. B-different coloring to depict the different domains in PI3K. C- Surface rendering showing binding site of GNP and Mg.
Source: Adapted from Pacold, M. , Suire, S. , Perisic, O. , Lara-Gonzalez, S. , Davis, C. , et al. (2000). Crystal structure and

Related Documents