Monoclonal antibodies specific for underphosphorylated retinoblastoma protein identify a cell cycle regulated phosphorylation site targeted by CDKs

作者: Tamara Zarkowska , Sally U , Ed Harlow , Sibylle Mittnacht

DOI: 10.1038/SJ.ONC.1200824

关键词: Cyclin-dependent kinaseCyclin-dependent kinase complexPhosphorylationE2FCyclin-dependent kinase 1BiologyProtein phosphorylationCyclin AMolecular biologyCyclin-dependent kinase 2

摘要: The growth suppressive activity of the retinoblastoma tumour suppressor protein is controlled by cell cycle dependent phosphorylation. However, while many in vivo phosphorylation sites have been mapped, identities those residues whose regulated remain elusive. We mapped epitopes three independent monoclonal antibodies that recognise a distinction between differentially phosphorylated pRB sub-populations. All an identical epitope which encompasses essential serine positioned within consensus site for proline directed kinase provide evidence this residue, 608 pRB, authentic can be vitro cyclin A-CDK2 and D1-CDK4 kinases but not E-CDK2 or mitogen activated ERK2. Phosphorylation at residue seems to regulated, occurring prior entry into S phase.

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