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PMID: 9761742 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Atypical protein kinase Clambda binds and regulates p70 S6 kinase.

The Biochemical journal ·Vol. 335 ( Pt 2) ·1998-10-15 ·Pages 417-24

Akimoto K, Nakaya M, Yamanaka T, Tanaka J, Matsuda S, Weng QP, Avruch J, Ohno S

Abstract

p70 S6 kinase (p70 S6K) has been implicated in the regulation of cell cycle progression. However, the mechanism of its activation is not fully understood. In the present work, evidence is provided that an atypical protein kinase C (PKC) isotype, PKClambda, is indispensable, but not sufficient, for the activation of p70 S6K. Both the regulatory and kinase domains of PKClambda associate directly with p70 S6K. Overexpression of the kinase domain without kinase activity or the regulatory domain of PKClambda results in the suppression of the serum-induced activation of p70 S6K. In addition, two types of dominant-negative mutants of PKClambda, as well as a kinase-deficient mutant of p70 S6K, suppress serum-induced DNA synthesis and E2F activation. The overexpresion of the active form of PKClambda, however, fails to activate p70 S6K. These results suggest that PKClambda is a mediator in the regulation of p70 S6K activity and plays an important role in cell cycle progression.

MeSH Terms
Amino Acid Sequence Animals Carrier Proteins Cell Cycle/drug effects,genetics Cell Cycle Proteins DNA-Binding Proteins E2F Transcription Factors Enzyme Activation Gene Expression Regulation Humans Isoenzymes Molecular Sequence Data Mutation Platelet-Derived Growth Factor/pharmacology Protein Kinase C/drug effects,genetics,metabolism Retinoblastoma-Binding Protein 1 Ribosomal Protein S6 Kinases/genetics,metabolism Sirolimus/pharmacology Transcription Factor DP1 Transcription Factors/genetics,metabolism
Chemicals
Carrier Proteins Cell Cycle Proteins DNA-Binding Proteins E2F Transcription Factors Isoenzymes Platelet-Derived Growth Factor Retinoblastoma-Binding Protein 1 Transcription Factor DP1 Transcription Factors Ribosomal Protein S6 Kinases Protein Kinase C protein kinase C lambda Sirolimus
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Akimoto K
Department of Molecular Biology, Yokohama City University School of Medicine, 3-9 Fuku-ura, Kanazawa-ku, Yokohama 236, Japan.
Nakaya M
Yamanaka T
Tanaka J
Matsuda S
Weng Q P
Avruch J
Ohno S
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Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
0264-6021
DOI
10.1042/bj3350417
Published
1998-10-15
Pages
417-24
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1219797
Subset
IM
Grants
NIDDK NIH HHS · DK17776 · United States
External Links
PubMed source DOI: 10.1042/bj3350417 PMC Full Text View journal details
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