A phospho-proteomic screen identifies novel S6K1 and mTORC1 substrates revealing additional complexity in the signaling network regulating cell growth

K Jastrzebski; KM Hannan; CM House; SSC Hung; RB Pearson; RD Hannan

Journal article

A phospho-proteomic screen identifies novel S6K1 and mTORC1 substrates revealing additional complexity in the signaling network regulating cell growth

K Jastrzebski, KM Hannan, CM House, SSC Hung, RB Pearson, RD Hannan

Cellular Signalling | ELSEVIER SCIENCE INC | Published : 2011

DOI: 10.1016/j.cellsig.2011.03.016

Abstract

S6K1, a critical downstream substrate of mTORC1, has been implicated in regulating protein synthesis and a variety of processes that impinge upon cell growth and proliferation. While the role of the cytoplasmic p70S6K1 isoform in the regulation of translation has been intensively studied, the targets and function of the nuclear p85S6K1 isoform remain unclear. Therefore, we carried out a phospho-proteomic screen to identify novel p85S6K1 substrates. Four novel putative p85S6K1 substrates, GRP75, CCTβ, PGK1 and RACK1, and two mTORC1 substrates, ANXA4 and PSMA6 were identified, with diverse roles in chaperone function, ribosome maturation, metabolism, vesicle trafficking and the proteasome, res..

View full abstract

University of Melbourne Researchers

Sandy Hung Author

Richard Pearson Author

Related Projects (3)

Novel regulation of rDNA transcription by mTOR/S6K signalling

Increased cellular growth requires a number of important processes to occur, the most fundamental of which is protein synthesis. Successful ..

AKT regulation of growth and proliferation

Ribosome synthesis and function is critical for normal cell growth and division and hence this process is exquisitely regulated. Conversely,..

"Deregulation of ribosome signalling, synthesis and function during malignant transformation."

A major feature of tumour progression is accelerated cell growth and protein synthesis. Moreover, increased synthesis of ribosomes (the prot..

Grants

Awarded by National Health and Medical Research Council

Funding Acknowledgements

The authors would like to acknowledge the technical assistance of Yvette Curlis in the acquisition of MS data as well as Dr Belinda Mitchell and Frosa Katsis (St Vincent's Institute of Medical Research, Australia) for carrying out phosphate release analysis. We would also like to thank Prof K.R. Willison, Dr J Grantham and EA McCormack for helpful discussions. This work was supported by grants from the National Health and Medical Research Council (NHMRC) of Australia to RDH (NHMRC #166908 and #251688) and to RBP (NHMRC #509087 and #400116), as well as Cancer Council Victoria funding to RBP.