CK2alpha-protein phosphatase 2A molecular complex: possible interaction with the MAP kinase pathway.
Despite its wide range of known substrates, the signaling function of protein kinase CK2 is still enigmatic. Mounting evidence suggests that CK2alpha, the catalytic subunit of holoenzymic CK2, may exist free of its usual regulatory partner CK2beta, raising the possibility that 'free' CK2alpha has regulation and function distinct from those of the holoenzyme. We previously reported that CK2alpha could bind to the core dimer of protein phosphatase 2A, and indirectly cause down-regulation of the PP2A substrate MEK1, possibly via activation of PP2A and/or targeting of PP2A to some element of the Ras/Raf/MEK pathway. Here, these results are confirmed and extended. By using transfection experiments and immune kinase assays, we show that endogenous PP2Ac and CK2beta are the only major substrates associating with epitope-tagged CK2alpha, and that expression of activated Raf results in disruption of the CK2alpha-PP2A association. Such disruption might be a necessary step for maximal activation of the MAP kinase pathway by Raf. In keeping with this idea, overexpression ofCK2alpha dose-dependently inhibits the mitogen-induced activation of cotransfected, epitope-tagged MAP kinase. We suggest that the CK2beta free form of CK2alpha is both a target and a regulator of Raf/MAPK signaling.
Lebrin
F
F
INSERM U244 and CEA/Grenoble, DBMS-BRCE, Grenoble, France.
Bianchini
L
L
Rabilloud
T
T
Chambaz
E M
EM
Goldberg
Y
Y
D016475:3T3 Cells; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047390:Casein Kinase II; D020134:Catalytic Domain; D051379:Mice; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D011485:Protein Binding; D054648:Protein Phosphatase 2; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*
D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2