Dr. Martha Robles Flores

rmartha@servidor.unam.mx

Molecular bases of protein kinase C activation

SUMMARY

Protein Kinase C (PKC) is an extremely important enzyme in the processes of hormone signal transduction, cell differentiation and tumorigenesis (1). This enzyme belongs to a family of serine-threonine kinases that are activated by acid phospholipids, by phosphatidylserine in particular, but that have different requirements of calcium, diacylglycerol and phorbol esters for their activation (1). In order to understand the action mechanism of the PKC isoforms, it is necessary to learn about their activation process. The precise molecular basis of this phenomenon is far from clear at present and constitutes a very active field of study. Furthermore, PKC translocation from the cytosol to the plasma membrane seems to be involved in its activation, down-regulation and access to specific substrates, but the molecular basis of this redistribution is also unknown. We have found that in rat hepatocytes, in vivo treatment with PMA (phorbol myristate acetate), the powerful tumor promoter, produces, among other effects, a rapid translocation of PKC isoforms to the plasma membrane accompanied by a rapid selective loss in activity of some of these PKC isoforms. We have also identified at least 7 proteins that bind only the active form of PKC (RACKs). The purpose of our study is to investigate the physiological meaning of and the molecular mechanisms involved in this paradoxical decrease in activity induced by the PMA activator, and the relation between translocation events and PKC activation.

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