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

被引：17

作者：

Jastrzebski, Katarzyna ^{[1
]}

Hannan, Katherine M. ^{[1
]}

House, Colin M. ^{[1
]}

Hung, Sandy S. -C. ^{[1
]}

Pearson, Richard B. ^{[1
,2
,3
]}

Hannan, Ross D. ^{[1
,2
,3
]}

机构：

[1] Peter MacCallum Canc Ctr, Div Res, Melbourne, Vic 8006, Australia

[2] Univ Melbourne, Dept Biochem & Mol Biol, Melbourne, Vic 3010, Australia

[3] Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia

来源：

CELLULAR SIGNALLING | 2011年 / 23卷 / 08期

基金：

英国医学研究理事会;

关键词：

S6K1; signaling; mTOR; Phospho-proteomics; Chaperonin; INDUCED PROTEIN-KINASE; MAMMALIAN TARGET; CYTOSKELETAL ORGANIZATION; EUKARYOTIC TRANSLATION; PHOSPHORYLATION SITES; MOLECULAR-MECHANISMS; PROTEASOMAL ATPASES; CYCLE PROGRESSION; CRYSTAL-STRUCTURE; CHAPERONIN CCT;

D O I：

10.1016/j.cellsig.2011.03.016

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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, CCT beta, 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 CCT beta, 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. (C) 2011 Elsevier Inc. All rights reserved.

引用

页码：1338 / 1347

页数：10

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