Atypical protein kinase Clambda binds and regulates p70 S6 kinase.
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.
Department of Molecular Biology, Yokohama City University School of Medicine, 3-9 Fuku-ura, Kanazawa-ku, Yokohama 236, Japan.
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K
Akimoto
M
M
Nakaya
T
T
Yamanaka
J
J
Tanaka
S
S
Matsuda
Q P
QP
Weng
J
J
Avruch
S
S
Ohno
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D006801:Humans; D007527:Isoenzymes; D008969:Molecular Sequence Data; D009154:Mutation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011493:Protein Kinase C / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D056465:Retinoblastoma-Binding Protein 1; D019893:Ribosomal Protein S6 Kinases / Q000235:genetics* / Q000378:metabolism*; D020123:Sirolimus / Q000494:pharmacology; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000099293:Protein Kinase C-lambda
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D007527:Isoenzymes; D010982:Platelet-Derived Growth Factor; D011493:Protein Kinase C; D056465:Retinoblastoma-Binding Protein 1; D019893:Ribosomal Protein S6 Kinases; D020123:Sirolimus; D050680:Transcription Factor DP1; D014157:Transcription Factors; D000099293:Protein Kinase C-lambda