Regulation and localization of ribosomal protein S6 kinase 1 isoforms

被引：26

作者：

Kim, Doyil ^{[1
]}

Akcakanat, Argun ^{[1
]}

Singh, Gopal ^{[1
]}

Sharma, Chandeshwar ^{[1
]}

Meric-Bernstam, Funda ^{[1
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA

来源：

GROWTH FACTORS | 2009年 / 27卷 / 01期

关键词：

mTOR; p85S6K1; p70S6K1; ribosomal S6 kinase; cell growth; MAMMALIAN TARGET; SERINE PHOSPHORYLATION; CELL-GROWTH; P70; ACTIVATION; RAPAMYCIN; MTOR; IDENTIFICATION; S6-KINASE-1; TRANSLATION;

D O I：

10.1080/08977190802556986

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Ribosomal protein S6 kinase 1 (S6K1), a critical mediator of cell growth, is overexpressed in breast cancer and is associated with poor prognosis. S6K1 has two known isoforms, p85(S6K1) and p70(S6K1). p85S6K1 is characterized by 23 additional amino acids in the N-terminus of p70S6K1. This is thought to target p85(S6K1) to the nucleus, while p70(S6K1) is mainly cytoplasmic. We sought to determine the activation, regulation, and function of p70(S6K1) and p85(S6K1) in breast cancer. We found that most breast cancer cell lines expressed both isoforms. Mitogen-dependent pathways concordantly regulated phosphorylation on T389, S371, and T421/S424. Phosphorylation of both isoforms was inhibited by PI3K/mTOR inhibitors. Mitogen-dependent pathways concordantly regulated the phosphorylation of the two isoforms on T389, S371, and T421/S424. Both isoforms had S6 kinase activity. We also detected a p60 isoform with antibodies to the p70S6K1 C-terminal but not the N-terminal. Further studies on S6K1 isoforms are warranted for therapeutically targeting this pathway.

引用

页码：12 / 21

页数：10

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