CONTROL OF PRB PHOSPHORYLATION

Two opposing enzymatic reactions control the activity of the retinobla stoma tumour suppressor protein, pRB. Phosphorylation inactivates pRB' s ability to sequester miscellaneous cellular proteins, mostly involve d in regulating gene transcription, whereas pRB dephosphorylation rest ores this ability. For some time now it has been suspected that member s of the cyclin/cyclin-dependent kinase (cyclin/cdk) family mediate pR B inactivation. Recent results indicate that pRB phosphorylation is no t executed by a single kinase but by a combination of cyclin/cdks, eac h one phosphorylating a subset of pRB's phosphorylation sites. The dif ferent kinases appear to be activated by growth factors through distin ct signal transduction pathways. This lends itself to an attractive mo del whereby pRB phosphorylation may constitute an integration point fo r these signalling pathways, perhaps allowing cell cycle progression o nly when concurrent activation of these signalling pathways has been a chieved.