Mitotic regulation of ribosomal protein S6 kinases

Jameel Shah

Appointment Period: 2000-2001 / Grant Year: [16]

My project during this training period involved the study of regulation of ribosomal protein S6 kinases during the mitotic phase of the mammalian cell cycle. The primary mechanism of mitotic control of S6 kinases appears to be through serine/threonine phosphorylation. Therefore, this project emphasized studying site-specific phosphorylation, which consequently is heavily proline-directed serine/threonine phosphorylation in mitosis. A study of candidate mitotic S6 kinases indicated that cdc2 is the likely mitotic S6 kinase.

PUBLICATIONS (resulting from this training, and some recent ones)

Shah OJ, Ghosh S, Hunter T. (2003) Mitotic regulation of ribosomal S6 kinase 1 involves Ser/Thr, Prophosphorylation of consensus and non-consensus sites by Cdc2. J Biol Chem 278:16433-42.

Shah OJ, Wang Z, Hunter T. (2004) Inappropriate activation of the TSC/Rheb/mTOR/S6K cassette induces IRS1/2depletion, insulin resistance, and cell survival deficiencies. Curr Biol 14:1650-6.

Shah OJ, Hunter T. (2004) Critical role of T-loop and H-motif phosphorylation in the regulation of S6kinase 1 by the tuberous sclerosis complex. J Biol Chem 279:20816-23.

Shah OJ, Hunter T. Tuberous sclerosis and insulin resistance. (2005) Unlikely bedfellows reveal a TORridaffair. Cell Cycle 4:46-51.

Shah OJ, Hunter T. (2006) Turnover of the active fraction of IRS1 involves raptor-mTOR- andS6K1-dependent serine phosphorylation in cell culture models of tuberous sclerosis. Mol Cell Biol 26:6425-34.

Han EK, Leverson JD, McGonigal T, Shah OJ, Woods KW, Hunter T, Giranda VL, Luo Y. (2007) Akt inhibitor A-443654 induces rapid Akt Ser-473 phosphorylation independent of mTORC1 inhibition. Oncogene. 2007 Mar 5; [Epub ahead of print]