Regulation of protein phosphatase 2A by direct interaction with casein kinase 2alpha.
Timely deactivation of kinase cascades is crucial to the normal control of cell signaling and is partly accomplished by protein phosphatase 2A (PP2A). The catalytic (alpha) subunit of the serine-threonine kinase casein kinase 2 (CK2) bound to PP2A in vitro and in mitogen-starved cells; binding required the integrity of a sequence motif common to CK2alpha and SV40 small t antigen. Overexpression of CK2alpha resulted in deactivation of mitogen-activated protein kinase kinase (MEK) and suppression of cell growth. Moreover, CK2alpha inhibited the transforming activity of oncogenic Ras, but not that of constitutively activated MEK. Thus, CK2alpha may regulate the deactivation of the mitogen-activated protein kinase pathway.
Hériché
J K
JK
Commissariat à l'Energie Atomique, Département de Biologie Moléculaire et Structurale, Laboratoire de Biochimie des Régulations Cellulaires Endocrines, Unité 244, F-38054 Grenoble Cédex 9, France.
Lebrin
F
F
Rabilloud
T
T
Leroy
D
D
Chambaz
E M
EM
Goldberg
Y
Y
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D000952:Antigens, Polyomavirus Transforming; D001665:Binding Sites; D047390:Casein Kinase II; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D048369:MAP Kinase Kinase 1; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases; D009154:Mutation; D019319:Okadaic Acid / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D054648:Protein Phosphatase 2; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism* / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection; D018631:ras Proteins / Q000494:pharmacology
D000952:Antigens, Polyomavirus Transforming; D010982:Platelet-Derived Growth Factor; D011993:Recombinant Fusion Proteins; D019319:Okadaic Acid; D011505:Protein-Tyrosine Kinases; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases; D048369:MAP Kinase Kinase 1; C482127:Map2k1 protein, mouse; D020929:Mitogen-Activated Protein Kinase Kinases; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; D018631:ras Proteins