Site-specific and temporally-regulated retinoblastoma protein dephosphorylation by protein phosphatase type 1

pRb is dephosphorylated at mitotic exit by the type 1 serine/threonine prot ein phosphatases (PP1), Here we demonstrate for the first time that mitotic pRb dephosphorylation is a sequential, temporally-regulated event. We also provide evidence that the three mammalian isoforms of PP1, alpha, gamma -1 , and delta, differ in their respective preferences for site-specific pRb d ephosphorylation and that the mitotic and G(1) PP1-isoform counterparts exh ibit differential activities towards mitotic pRb, Finally, the physiologica l relevance of the striking contrast between the patterns of Thr821 and Thr 826 dephosphorylation, sites known to be important for disrupting binding o f LXCXE-containing proteins to pRb, is addressed.