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to Bad1


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Department of Immunology and Oncology, Centro Nacional de Biotecnología, Campus de Cantoblanco, Madrid, Spain;
Laboratoire de Physiologie de la Reproduction, Centre National de la Recherche Scientifique, Institut National de la Recherche Agronomique, Paris, France; and
Département dImmunologie, Laboratoire de Signalisation Immunoparasitaire, Institut Pasteur, Paris, France
The diverse forms of protein phosphatase 1 (PP1) in vivo result
from the association of the catalytic subunit with different regulatory
subunits. We recently have described that PP1
is a Ras-activated Bad
phosphatase that regulates IL-2 deprivation-induced apoptosis. With the
yeast two-hybrid system, GST fusion proteins, indirect
immunofluorescence, and coimmunoprecipitation, we found that Bcl-2
interacts with PP1
and Bad. In contrast, Bad did not interact with
14-3-3 protein. Bcl-2 depletion decreased phosphatase activity and
association of PP1
to Bad. Bcl-2 contains the RIVAF motif, analogous
to the well characterized R/KXV/IXF consensus motif shared by most
PP1-interacting proteins. This sequence is involved in the binding of
Bcl-2 to PP1
. Disruption of Bcl-2/PP1
association strongly
decreased Bcl-2 and Bad-associated phosphatase activity and formation
of the trimolecular complex. These results suggest that Bcl-2 targets
PP1
to Bad.
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