Naturally occurring protein kinase activators

Phospholipase C, which occurs in different subtypes in the cell, is a key enzyme of phosphatide inositol metabohsm (for cleavage specificity, see Fig. 5.24). Two central signaling pathways regulate phosphohpase C activity of the cell in a positive way (Fig. 6.4). Phospholipases of type CP (PL-CP) are activated by G-proteins and are thus linked into signal pathways starting from G-protein-coupled receptors. Phosphohpases of type Y (PL-Cy), in contrast, are activated by transmembrane receptors with intrinsic or associated tyrosine kinase activity (see Chapter 8, Chapter 10). The nature of the extracellular stimuli activated by the two major reaction pathways is very diverse (see Fig 6.4), which is why the phosphohpase C activity of the cell is subject to multiple regulation. 

After PMA treatment the recovery of protein kinase C in the homogenate is 100% when compared to the control homogenate. However, a redistribution of protein kinase C has occurred. Upon activation of protein kinase C by PMA (or by its natural activators DAG and Ca2+ ions) protein kinase C is translocated to the plasma membrane where it phosphorylates protein targets. 

Many opium-derived and other IQs are psychoactive, the best known being the analgesic, addictive, narcotic, opium-derived morphinan alkaloids codeine and morphine (heroin being the semi-synthetic diacetate of morphine). The tertiary or quaternary amine structural component is important for the activity of some Erytkrina alkaloids and bisbenzyliso-quinolines (notably the major curare component (+)-tubocurarine) as antagonists of the nACh-R involved in neuronal excitation of skeletal muscle. The planar disposition of some polycyclic benzophenanthridines enables intercalation (parallel interleaving) between the base pairs of DNA. A variety of naturally occurring and synthetic IQ compounds are protein kinase inhibitors. 

Bryostatins are naturally occurring antineoplastic macro-cyclic lactones derived from the marine invertebrate Bugula neritina, different varieties being isolated from different populations of the same species. More than 13 structurally related compounds have been isolated (1,2), and there is a variety of synthetic analogues (3). The bryostatins modulate the activity of protein kinase C. 

Naturally occurring flavonoids, such as quercetin and genistein, inhibit tyrosine kinase activity by competing with ATP (Akiyama et al., 1987), and have been shown to inhibit cAMP-dependent protein kinase, PKC, and other ATP-requiring enzymes (Gazit et al.,... 

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