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.
PARTICIPANTS
- Ericka Patricia Rendón Huerta, M.Sc.
- Ma. Magdalena Hernández Alvarez, B.Sc.
- Hector Gonzales Aguilar, B.Sc.
BIBLIOGRAPHY
-
1. Robles-Flores, M., Alcántara-Hernández, R. and García-Sáinz,
J.A. (1991) Differences in phorbol ester-induced decrease of the activity
of protein kinase C isozymes in rat hepatocytes. Biochim. Biophys. Acta
1094: 77-84.
- 2. Robles-Flores, M. and García-Sáinz, J.A. (1993) Activated
protein kinase C binds to intracellular receptors in rat hepatocytes. Biochem.
J. 296: 467-472.
- 3. Robles-Flores, M. and García-Sáinz, J.A., (1994) Immunological
cross-reactivity of G- protein b, subunit and receptor for activated C-kinase.
Biochem. Mol. Biol, Int. 34: (3): 465-473.
- 4. Robles-Flores, M. and García-Sáinz, J.A. (1995) Cross-talk
between glycagon- and adenosine-mediated signalling systems in rat hepatocytes:
effects on cyclic AMP- phosphodiesterase activity. Biochem. J. 312:
(3): 763-767.
Back to Researchers