Preferences for phosphorylation sites in the retinoblastoma protein of D-type cyclin-dependent kinases, Cdk4 and Cdk6, in vitro

Tohru Takaki, Kazuhiro Fukasawa, Ikuko Suzuki-Takahashi, Kentaro Senba, Masatoshi Kitagawa, Yoichi Taya, Hiroshi Hirai

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

D-type cyclin-dependent kinases (Cdk4 and Cdk6) regulate the G1 to S phase progression of the mammalian cell cycle. It has been suggested that Cdk4 and Cdk6 may have distinct functions in vivo, even though they are indistinguishable biochemically. Here we show that although these Cdks phosphorylate multiple residues in pRB, they do so with different residue selectivities in vitro; Thr821 and Thr826 are preferentially phosphorylated by Cdk6 and Cdk4, respectively. This raises the possibility different substrate specificities lead to their different roles in the regulation of cellular events. Furthermore, our results indicate the new concept that Cdk itself contributes to substrate recognition.

Original languageEnglish
Pages (from-to)381-386
Number of pages6
JournalJournal of Biochemistry
Volume137
Issue number3
DOIs
Publication statusPublished - 2005 Mar
Externally publishedYes

Fingerprint

Cyclin-Dependent Kinase 4
Cyclin D
Retinoblastoma Protein
Phosphorylation
Substrate Specificity
S Phase
Cell Cycle
Substrates
Cells
In Vitro Techniques

Keywords

  • Cdk4
  • Cdk6
  • Phosphorylation
  • pRB

ASJC Scopus subject areas

  • Biochemistry

Cite this

Preferences for phosphorylation sites in the retinoblastoma protein of D-type cyclin-dependent kinases, Cdk4 and Cdk6, in vitro. / Takaki, Tohru; Fukasawa, Kazuhiro; Suzuki-Takahashi, Ikuko; Senba, Kentaro; Kitagawa, Masatoshi; Taya, Yoichi; Hirai, Hiroshi.

In: Journal of Biochemistry, Vol. 137, No. 3, 03.2005, p. 381-386.

Research output: Contribution to journalArticle

Takaki, Tohru ; Fukasawa, Kazuhiro ; Suzuki-Takahashi, Ikuko ; Senba, Kentaro ; Kitagawa, Masatoshi ; Taya, Yoichi ; Hirai, Hiroshi. / Preferences for phosphorylation sites in the retinoblastoma protein of D-type cyclin-dependent kinases, Cdk4 and Cdk6, in vitro. In: Journal of Biochemistry. 2005 ; Vol. 137, No. 3. pp. 381-386.
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