Phosphatidyl inositol phosphate-activated protein kinase

The following effects take place because the receptors are coupled to adenylyl cyclase or to phospholipase C. Adenylyl cyclase catalyzes the synthesis of cAMP, while phospholipase C catalyzes the hydrolysis of the phosphatidyl-4,5-bisphos-phate, releasing inositol-l,4,5-trisphosphate (IP3). This IP3, in turn, travels to the endoplasmic reticulum, where it provokes the momentary release of calcium ions. The increase in Ca " ion levels, in turn, provokes activation of a number of protein kinases, as discussed in the Calcium and Phosphate section. All of these receptors are polypeptides that weave seven times in or out of the plasma membrane. All of these receptors are directly linked to G protein, and require G protein for transmitting their message within the membrane to various enzymes. 

Phosphatidyl inositol, which is present in the inner leaflet of the plasma membrane, is convated to PM,5-bisP by kinases that phosphorylate the inositol ring at the 4 and 5 positions (Fig. 11.12). PM,5-bisP, which has three phosphate groups, is cleaved by a phospholipase C-isozyme to generate IP3 and DAG. The phospholipase isozyme C., (PLC.,) is activated by tyrosine kinase growth factor receptors, and phospholipase C 3 is activated by a heptahelical receptor-G protein signal ffansduction pathway. 

Figure 50. PTEN. The tumor suppressor gene and gene product protein PTEN (phosphatase tensin homolog deleted on chromosome ten, human 10q23.3) (Table VIII), is the natural inhibitor of oncogenes PI3K/Akt (phosphatidyl inositol kinase 3 protein kinase 3 phosphatidylinositol 3 phosphate Jacob Furth s AK mouse strain thymic lymphoma retroviral oncogene phosphoinosite-dependent kinase). The PTEN protein inactivates PIP3 by dephosphorylation PDKl (phosphoinositol-dependent kinase) is not recruited to the plasma membrane to activate Akt by phosphorylation. Sarah M. Planchon et al. The nuclear affairs of PTEN. J Cell Sci 2008 121 249-253. doi 10.1242/jcs.022459...

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