Bcl-2 Targets Protein Phosphatase 1α to Bad

Abstract

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 PP1α 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 PP1α and Bad. In contrast, Bad did not interact with 14-3-3 protein. Bcl-2 depletion decreased phosphatase activity and association of PP1α 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 PP1α. Disruption of Bcl-2/PP1α association strongly decreased Bcl-2 and Bad-associated phosphatase activity and formation of the trimolecular complex. These results suggest that Bcl-2 targets PP1α to Bad.

Segregation of Bad from Lipid Rafts Is Implicated in the Induction of Apoptosis

“…It has been shown that the association of 14-3-3 protein with Bad is dependent on serine 155 phosphorylation of Bad. In agreement, IL-2-stimulation of a murine T cell line induces serine 112 and 136 phosphorylation of Bad without association with 14-3-3 protein (4).…”

Gene amplification and overexpression of protein phosphatase 1α in oral squamous cell carcinoma cell lines

“…It has been demonstrated that PP1a can dephosphorylate the tumor suppressors pRB (Alberts et al, 1993;Durfee et al, 1993) and BRCA1 (Liu et al, 2002), suggesting its involvement in regulating cell cycle checkpoint control function of these tumor suppressors. Protein phosphatase 1a also interacts with Bcl-2, which targets PP1a to dephosphorylate Bad, and may play a role in regulating apoptosis (Ayllon et al, 2001). It has been reported that PP1a is upregulated and PP1 activity is significantly higher in preneoplastic lesions of the liver as well as in hepatomas, suggesting that PP1a may be involved in hepatocarcinogenesis (Saadat et al, 1995;Imai et al, 1999).…”

Effect of Buspirone, Fluoxetine and 8-OH-DPAT on Striatal Expression of Bax, Caspase-3 and Bcl-2 Proteins in 6-Hydroxydopamine-Induced Hemi-Parkinsonian Rats

“…This is in agreement with previous studies showing an over expression of Bax protein in parkinsonian patients 18 and 6-OHDA-treated rats. [19][20] In those groups of parkinsonian rats which were treated sub-chronically by buspirone, fluoxetine and 8-OH-DPAT, striatal expression of Bax protein was dropped markedly to the level of control group. The attenuating effect of buspirone and 8-OH-DPAT on expression of Bax Protein was greater than fluoxetine.…”