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PMID: 9560223 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Targeted disruption of p70(s6k) defines its role in protein synthesis and rapamycin sensitivity.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 95 ·No. 9 ·1998-04-28 ·Pages 5033-8

Kawasome H, Papst P, Webb S, Keller GM, Johnson GL, Gelfand EW, Terada N

Abstract

Here, we disrupted the p70 S6 kinase (p70(s6k)) gene in murine embryonic stem cells to determine the role of this kinase in cell growth, protein synthesis, and rapamycin sensitivity. p70(s6k-/-) cells proliferated at a slower rate than parental cells, suggesting that p70(s6k) has a positive influence on cell proliferation but is not essential. In addition, rapamycin inhibited proliferation of p70(s6k-/-) cells, indicating that other events inhibited by the drug, independent of p70(s6k), also are important for both cell proliferation and the action of rapamycin. In p70(s6k-/-) cells, which exhibited no ribosomal S6 phosphorylation, translation of mRNA encoding ribosomal proteins was not increased by serum nor specifically inhibited by rapamycin. In contrast, rapamycin inhibited phosphorylation of initiation factor 4E-binding protein 1 (4E-BP1), general mRNA translation, and overall protein synthesis in p70(s6k-/-) cells, indicating that these events proceed independently of p70(s6k) activity. This study localizes the function of p70(s6k) to ribosomal biogenesis by regulating ribosomal protein synthesis at the level of mRNA translation.

MeSH Terms
Adaptor Proteins, Signal Transducing Amino Acid Sequence Animals Carrier Proteins Cell Cycle Proteins Cell Division Eukaryotic Initiation Factors Mice Molecular Sequence Data Mutagenesis, Insertional Phosphoproteins/metabolism Phosphorylation Polyenes/pharmacology Protein Biosynthesis/drug effects RNA, Messenger/genetics Ribosomal Protein S6 Ribosomal Protein S6 Kinases/physiology Ribosomal Proteins/biosynthesis,metabolism Sirolimus
Chemicals
Adaptor Proteins, Signal Transducing Carrier Proteins Cell Cycle Proteins Eif4ebp1 protein, mouse Eukaryotic Initiation Factors Phosphoproteins Polyenes RNA, Messenger Ribosomal Protein S6 Ribosomal Proteins Ribosomal Protein S6 Kinases Sirolimus
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Kawasome H
Division of Basic Sciences, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.
Papst P
Webb S
Keller G M
Johnson G L
Gelfand E W
Terada N
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.95.9.5033
Published
1998-04-28
Pages
5033-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC20208
Subset
IM
Grants
NHLBI NIH HHS · P01 HL036577 · United States
NCI NIH HHS · CA-64685 · United States
NHLBI NIH HHS · HL-36577 · United States
Databases
GENBANK
AB015196, AB015197
External Links
PubMed source DOI: 10.1073/pnas.95.9.5033 PMC Full Text View journal details
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