TY - JOUR
T1 - A phospho-proteomic screen identifies novel S6K1 and mTORC1 substrates revealing additional complexity in the signaling network regulating cell growth
AU - Jastrzebski, Katarzyna
AU - Hannan, Katherine M
AU - House, Colin M
AU - Hung, Sandy S-C
AU - Pearson, Richard
AU - Hannan, Ross
PY - 2011
Y1 - 2011
N2 - 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 p70(S6K1) isoform in the regulation of translation has been intensively studied, the targets and function of the nuclear p85(S6K1) isoform remain unclear. Therefore, we carried out a phospho-proteomic screen to identify novel p85(S6K1) substrates. Four novel putative p85(S6K1) substrates, GRP75, CCTbeta, 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, respectively. The chaperonin subunit CCTbeta was further investigated and the site of phosphorylation mapped to serine 260, a site located in the chaperonin apical domain. Consistent with this domain being involved in folding substrate interactions, we found that phosphorylation of serine 260 modulates chaperonin folding activity.
AB - 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 p70(S6K1) isoform in the regulation of translation has been intensively studied, the targets and function of the nuclear p85(S6K1) isoform remain unclear. Therefore, we carried out a phospho-proteomic screen to identify novel p85(S6K1) substrates. Four novel putative p85(S6K1) substrates, GRP75, CCTbeta, 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, respectively. The chaperonin subunit CCTbeta was further investigated and the site of phosphorylation mapped to serine 260, a site located in the chaperonin apical domain. Consistent with this domain being involved in folding substrate interactions, we found that phosphorylation of serine 260 modulates chaperonin folding activity.
UR - http://www.ncbi.nlm.nih.gov/pubmed/21440620
U2 - 10.1016/j.cellsig.2011.03.016
DO - 10.1016/j.cellsig.2011.03.016
M3 - Article
VL - 23
SP - 1338
EP - 1347
JO - Cellular Signalling
JF - Cellular Signalling
SN - 0898-6568
IS - 8
ER -