PMID- 12062056 OWN - NLM STAT- MEDLINE DCOM- 20021209 LR - 20211203 IS - 0960-9822 (Print) IS - 0960-9822 (Linking) VI - 12 IP - 11 DP - 2002 Jun 4 TI - A role for PI 3-kinase and PKB activity in the G2/M phase of the cell cycle. PG - 919-24 AB - The role of the PI 3-kinase cascade in regulation of cell growth is well established [1]. PKB (protein kinase B) is a key downstream effector of the PI 3-kinase pathway and is best known for its antiapoptotic effects [2,3] and the role it plays in initiation of S phase [4]. Here, we show that PKB activity is high in the G2/M phase of the cell cycle in epithelial cells. Inhibition of the PI 3-kinase pathway in MDCK cells induces apoptosis at the G2/M transition, prevents activation of cyclin B-associated kinase, and prohibits entry of the surviving cells into mitosis. All of these consequences of the inhibition of PI 3-kinase are relieved by expression of a constitutively active form of PKB (caPKB), indicating that PKB plays a role in regulation of the G2/M phase. Inhibition of PI 3-kinase results in activation of Chk1, whereas caPKB inhibits the ability of Chk1 to become activated in response to treatment with hydroxyurea. Preliminary data show that PKB phosphorylates the Chk1 polypeptide in vitro on serine 280. These results not only implicate PKB activity in transition through the G2/M stage of the cell cycle, but they also suggest the existence of crosstalk between the PI 3-kinase pathway and the key regulators of the DNA damage checkpoint machinery. FAU - Shtivelman, Emma AU - Shtivelman E AD - Cancer Research Institute, University of California-San Francisco, San Francisco, CA 94143-0128, USA. shtivelman@cc.ucsf.edu FAU - Sussman, Joshua AU - Sussman J FAU - Stokoe, David AU - Stokoe D LA - eng GR - R01 CA 79548/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - Curr Biol JT - Current biology : CB JID - 9107782 RN - 0 (Phosphoinositide-3 Kinase Inhibitors) RN - 0 (Proto-Oncogene Proteins) RN - EC 2.7.- (Protein Kinases) RN - EC 2.7.11.1 (CHEK1 protein, human) RN - EC 2.7.11.1 (Checkpoint Kinase 1) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - Animals MH - Cattle MH - Checkpoint Kinase 1 MH - *G2 Phase MH - HeLa Cells MH - Humans MH - *Mitosis MH - Phosphatidylinositol 3-Kinases/*metabolism MH - Phosphoinositide-3 Kinase Inhibitors MH - Protein Kinases/metabolism MH - *Protein Serine-Threonine Kinases MH - Proto-Oncogene Proteins/*metabolism MH - Proto-Oncogene Proteins c-akt EDAT- 2002/06/14 10:00 MHDA- 2002/12/10 04:00 CRDT- 2002/06/14 10:00 PHST- 2002/06/14 10:00 [pubmed] PHST- 2002/12/10 04:00 [medline] PHST- 2002/06/14 10:00 [entrez] AID - S0960-9822(02)00843-6 [pii] AID - 10.1016/s0960-9822(02)00843-6 [doi] PST - ppublish SO - Curr Biol. 2002 Jun 4;12(11):919-24. doi: 10.1016/s0960-9822(02)00843-6.