1. Atypical protein kinase Cλ binds and regulates p70 S6 kinase
- Author
-
Joseph Avruch, Junpei Tanaka, Kazunori Akimoto, Qing Ping Weng, Tomoyuki Yamanaka, Shin Ichi Matsuda, Shigeo Ohno, and Masa Aki Nakaya
- Subjects
Molecular Sequence Data ,Cell Cycle Proteins ,chemical and pharmacologic phenomena ,Mitogen-activated protein kinase kinase ,Biochemistry ,MAP2K7 ,Animals ,Humans ,ASK1 ,Amino Acid Sequence ,Kinase activity ,Molecular Biology ,Protein Kinase C ,Platelet-Derived Growth Factor ,Sirolimus ,MAP kinase kinase kinase ,biology ,Cyclin-dependent kinase 4 ,Ribosomal Protein S6 Kinases ,Cell Cycle ,Cyclin-dependent kinase 2 ,hemic and immune systems ,Cell Biology ,E2F Transcription Factors ,Cell biology ,DNA-Binding Proteins ,Enzyme Activation ,Isoenzymes ,Gene Expression Regulation ,Mutation ,biology.protein ,lipids (amino acids, peptides, and proteins) ,Cyclin-dependent kinase 9 ,Carrier Proteins ,Transcription Factor DP1 ,Retinoblastoma-Binding Protein 1 ,Transcription Factors ,Research Article - 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.
- Published
- 1998