Raf-1-associated protein phosphatase 2A as a positive regulator of kinase activation.

Article Details

Citation

Abraham D, Podar K, Pacher M, Kubicek M, Welzel N, Hemmings BA, Dilworth SM, Mischak H, Kolch W, Baccarini M

Raf-1-associated protein phosphatase 2A as a positive regulator of kinase activation.

J Biol Chem. 2000 Jul 21;275(29):22300-4.

PubMed ID
10801873 [ View in PubMed
]
Abstract

The Raf-1 kinase plays a key role in relaying proliferation signals elicited by mitogens or oncogenes. Raf-1 is regulated by complex and incompletely understood mechanisms including phosphorylation. A number of studies have indicated that phosphorylation of serines 259 and 621 can inhibit the Raf-1 kinase. We show that both serines are hypophosphorylated during early mitogenic stimulation and that hypophosphorylation correlates with peak Raf-1 activation. Concentrations of okadaic acid that selectively inhibit protein phosphatase 2A (PP2A) induce phosphorylation of these residues and prevent maximal activation of the Raf-1 kinase. This effect is mediated via phosphorylation of serine 259. The PP2A core heterodimer forms complexes with Raf-1 in vivo and in vitro. These data identify PP2A as a positive regulator of Raf-1 activation and are the first indication that PP2A may support the activation of an associated kinase.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
RAF proto-oncogene serine/threonine-protein kinaseP04049Details
Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoformP67775Details