Regulation and localization of ribosomal protein S6 kinase 1 isoforms

Doyil Kim; Argun Akcakanat; Gopal Singh; Chandeshwar Sharma; Funda Meric-Bernstam

doi:10.1080/08977190802556986

Regulation and localization of ribosomal protein S6 kinase 1 isoforms

Doyil Kim, Argun Akcakanat, Gopal Singh, Chandeshwar Sharma, Funda Meric-Bernstam

Research output: Contribution to journal › Article › peer-review

32 Scopus citations

Abstract

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. p85^S6K1 is characterized by 23 additional amino acids in the N-terminus of p70^S6K1. This is thought to target p85^S6K1 to the nucleus, while p70S6K1 is mainly cytoplasmic. We sought to determine the activation, regulation, and function of p70S6K1 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 p70^S6K1 C-terminal but not the N-terminal. Further studies on S6K1 isoforms are warranted for therapeutically targeting this pathway.

Original language	English (US)
Pages (from-to)	12-21
Number of pages	10
Journal	Growth Factors
Volume	27
Issue number	1
DOIs	https://doi.org/10.1080/08977190802556986
State	Published - 2009

Keywords

Cell growth
Ribosomal S6 kinase
mTOR
p70S6K1
p85S6K1

ASJC Scopus subject areas

Endocrinology
Clinical Biochemistry
Cell Biology

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10.1080/08977190802556986

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title = "Regulation and localization of ribosomal protein S6 kinase 1 isoforms",

abstract = "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, p85S6K1 and p70S6K1. p85S6K1 is characterized by 23 additional amino acids in the N-terminus of p70S6K1. This is thought to target p85S6K1 to the nucleus, while p70S6K1 is mainly cytoplasmic. We sought to determine the activation, regulation, and function of p70S6K1 and p85S6K1 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.",

keywords = "Cell growth, Ribosomal S6 kinase, mTOR, p70S6K1, p85S6K1",

author = "Doyil Kim and Argun Akcakanat and Gopal Singh and Chandeshwar Sharma and Funda Meric-Bernstam",

note = "Funding Information: This work was supported by a P50CA116199 grant from the National Cancer Institute (to Gabriel Hortobagyi, with a developmental project to FM-B), funding from the Gilson-Longenbough Foundation (to FM-B), an NIH1 R01 CA112199 grant (to FM-B), and the Cancer Center Core Grant CA16672 (to The University of Texas M. D. Anderson Cancer Center).",

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T1 - Regulation and localization of ribosomal protein S6 kinase 1 isoforms

AU - Kim, Doyil

AU - Akcakanat, Argun

AU - Singh, Gopal

AU - Sharma, Chandeshwar

AU - Meric-Bernstam, Funda

N1 - Funding Information: This work was supported by a P50CA116199 grant from the National Cancer Institute (to Gabriel Hortobagyi, with a developmental project to FM-B), funding from the Gilson-Longenbough Foundation (to FM-B), an NIH1 R01 CA112199 grant (to FM-B), and the Cancer Center Core Grant CA16672 (to The University of Texas M. D. Anderson Cancer Center).

PY - 2009

Y1 - 2009

N2 - 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, p85S6K1 and p70S6K1. p85S6K1 is characterized by 23 additional amino acids in the N-terminus of p70S6K1. This is thought to target p85S6K1 to the nucleus, while p70S6K1 is mainly cytoplasmic. We sought to determine the activation, regulation, and function of p70S6K1 and p85S6K1 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.

AB - 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, p85S6K1 and p70S6K1. p85S6K1 is characterized by 23 additional amino acids in the N-terminus of p70S6K1. This is thought to target p85S6K1 to the nucleus, while p70S6K1 is mainly cytoplasmic. We sought to determine the activation, regulation, and function of p70S6K1 and p85S6K1 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.

KW - Cell growth

KW - Ribosomal S6 kinase

KW - mTOR

KW - p70S6K1

KW - p85S6K1

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Regulation and localization of ribosomal protein S6 kinase 1 isoforms

Abstract

Keywords

ASJC Scopus subject areas

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