Pim-1 kinase promotes inactivation of the pro-apoptotic Bad protein by phosphorylating it on the Ser112 gatekeeper site.
Constitutive expression of the Pim-1 kinase prolongs survival of cytokine-deprived FDCP1 cells, partly via maintenance of Bcl-2 expression. Here, we show that Pim-1 colocalizes and physically interacts with the pro-apoptotic Bad protein and phosphorylates it in vitro on serine 112, which is a gatekeeper site for its inactivation. Furthermore, wild-type Pim-1, but not a kinase-deficient mutant, enhances phosphorylation of this site in FDCP1 cells and protects cells from the pro-apoptotic effects of Bad. Our results suggest that phosphorylation of Bad by Pim-1 is one of several mechanisms via which the Pim-1 kinase can enhance Bcl-2 activity and promote cell survival.
Aho
Teija L T
TL
Turku Centre for Biotechnology, University of Turku/Abo Akademi University, Tykistökatu 6 B, 20520 Turku, Finland.
Sandholm
Jouko
J
Peltola
Katriina J
KJ
Mankonen
Harri P
HP
Lilly
Michael
M
Koskinen
Päivi J
PJ
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D019556:COS Cells; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002522:Chlorocebus aethiops; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D007377:Interleukin-3 / Q000494:pharmacology; D007700:Kinetics; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051573:Proto-Oncogene Proteins c-pim-1; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection; D051025:bcl-Associated Death Protein
D002352:Carrier Proteins; D007377:Interleukin-3; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D051025:bcl-Associated Death Protein; D010768:Phosphoserine; D005982:Glutathione Transferase; D017346:Protein Serine-Threonine Kinases; D051573:Proto-Oncogene Proteins c-pim-1