Science · 1997 · 271 citations · 22 references
Life SciencesBiochemistryMolecular BiologyCell SignalingOncogenesSignal TransductionOncogenic ProliferationOncogenic Signaling PathwaysProtein Kinase CascadesProtein Phosphatase SignalingProto-oncogene ActivationRas Family OncogenesCasein Kinase RegulationCell Growth RegulationMitogen-activated Protein Kinase CascadesMitogen-activated Protein Kinase InactivationMitogen-activated Protein Kinase KinaseMitogen-activated Protein Kinase PathwaysOncogenic Ras SignalingProtein Phosphatase 2A Regulation
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.
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Transformation of Mammalian Cells by Constitutively Active MAP Kinase Kinase
Sam J. Mansour, Wayne T. Matten, April S. Hermann et al. · Science · 1994 · 1.4K citations