pRb phosphorylation is regulated differentially by cyclin-dependent kinase (Cdk) 2 and Cdk4 in retinoic acid-induced neuronal differentiation of P19 cells

Yumi Watanabe, Takeshi Watanabe, Masatoshi Kitagawa, Yoichi Taya, Keiichi Nakayama, Noboru Motoyama

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

The retinoblastoma protein (pRb) is a key regulator of cell growth, differentiation and survival. pRb(-/-) mice show abnormal neuronal cell death in the developing brain. The function of pRb is regulated by its phosphorylation state. In this study, the phosphorylation of pRb during retinoic acid (RA)-induced neuronal differentiation of P19 cells was examined using site-specific antibodies against pRb phosphorylated at Ser601, Ser605 and Ser773. Although pRb was hyperphosphorylated in undifferentiated P19 cells, Ser601 and Ser773 were not phosphorylated. Upon exposure to RA, however, these two sites became strongly phosphorylated. Cdk4 kinase activity was almost undetectable in undifferentiated P19 cells, but was strongly activated on exposure to RA. In contrast, Cdk2 kinase activity and the phosphorylation of Ser605 were observed in undifferentiated cells as well as in RA-treated cells. These observations suggest that Cdk2 and Cdk4 may phosphorylate different sites of pRb in vivo and that the two sites of pRb examined here are newly phosphorylated during RA-induced neuronal differentiation in P19 cells.

Original languageEnglish
Pages (from-to)342-350
Number of pages9
JournalBrain Research
Volume842
Issue number2
DOIs
Publication statusPublished - Sep 25 1999

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Cyclin-Dependent Kinase 2
Tretinoin
Cell Differentiation
Phosphorylation
Phosphotransferases
Retinoblastoma Protein
Cell Survival
Cell Death
Antibodies
Brain
Growth

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Cite this

pRb phosphorylation is regulated differentially by cyclin-dependent kinase (Cdk) 2 and Cdk4 in retinoic acid-induced neuronal differentiation of P19 cells. / Watanabe, Yumi; Watanabe, Takeshi; Kitagawa, Masatoshi; Taya, Yoichi; Nakayama, Keiichi; Motoyama, Noboru.

In: Brain Research, Vol. 842, No. 2, 25.09.1999, p. 342-350.

Research output: Contribution to journalArticle

Watanabe, Yumi ; Watanabe, Takeshi ; Kitagawa, Masatoshi ; Taya, Yoichi ; Nakayama, Keiichi ; Motoyama, Noboru. / pRb phosphorylation is regulated differentially by cyclin-dependent kinase (Cdk) 2 and Cdk4 in retinoic acid-induced neuronal differentiation of P19 cells. In: Brain Research. 1999 ; Vol. 842, No. 2. pp. 342-350.
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