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When deprived of anchorage to the extracellular matrix, fibroblasts arrest in G 1 phase at least in part due to inactivation of G 1 cyclin-dependent kinases. Despite great effort, how anchorage signals control the G 1 -S transition of fibroblasts remains highly elusive. We recently found that the mammalian target of rapamycin (mTOR) cascade might convey an anchorage signal that regulates S phase entry. Here, we show that Rhoassociated kinase connects this signal to the TSC1/TSC2-RHEB-mTOR pathway. Expression of a constitutively active form of ROCK1 suppressed all of the anchorage deprivation effects suppressible by tsc2 mutation in rat embryonic fibroblasts. TSC2 contains one evolutionarily conserved ROCK target-like sequence, and an alanine substitution for Thr 1203 in this sequence severely impaired the ability of ROCK1 to counteract the anchorage loss-imposed down-regulation of both G 1 cell cycle factors and mTORC1 activity. Moreover, TSC2 Thr 1203 underwent ROCK-dependent phosphorylation in vivo and could be phosphorylated by bacterially expressed active ROCK1 in vitro, providing biochemical evidence for a direct physical interaction between ROCK and TSC2.

MINT‐7890626: cdc27 (uniprotkb:Q4V8A2) physically interacts (MI:0915) with Cyclin‐A (uniprotkb:Q6AY13) by anti bait coimmunoprecipitation (MI:0006)

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