Inhibition of G1 cyclin expression in normal rat kidney cells by inostamycin, a phosphatidylinositol synthesis inhibitor

Atsuko Deguchi, Masaya Imoto, Kazuo Umezawa

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

We previously reported that inostamycin, an inhibitor of CDP-DG:inositol transferase, inhibited cell proliferation in normal rat kidney (NRK) cells by blocking cell cycle progression at the G1 phase. In the present paper, we report the effect of inostamycin on the serum-induced activation of Ser/Thr protein kinases that are involved in G1 progression. In quiescent NRK cells mitogen-activated protein kinase (MAP kinase) and casein kinase II were activated within 15 min after serum addition. Neither activation was affected by the treatment with inostamycin. However, in the inostamycin-treated cell, cyclin-dependent kinase 2 (CDK2) failed to be activated after serum stimulation. Since serum-induced expression of cyclin E was also suppressed by inostamycin, this inhibitor would appear to block CDK2 activation by inhibiting cyclin E expression. Furthermore, inostamycin also inhibited cyclin D1 expression induced by serum; and consequently, hyperphosphorylation of retinoblastoma protein (pRB) by RB-kinases such as CDK4 and CDK2 was abolished, which would result in elimination of functional inactivation of pRB. Thus, early G1 arrest in NRK cells by inostamycin is due to the inhibition of cyclin D1 and E expressions.

Original languageEnglish
Pages (from-to)1118-1122
Number of pages5
JournalJournal of Biochemistry
Volume120
Issue number6
Publication statusPublished - 1996 Dec

Fingerprint

Cyclin G1
Phosphatidylinositols
Rats
Kidney
Cyclin-Dependent Kinase 2
Cyclin E
Serum
Chemical activation
Cyclin D1
CDP-Diacylglycerol-Inositol 3-Phosphatidyltransferase
Cells
Casein Kinase II
Retinoblastoma Protein
Mitogen-Activated Protein Kinase Kinases
Cell proliferation
G1 Phase
inostamycin
Protein Kinases
Cell Cycle
Phosphotransferases

Keywords

  • cdk2
  • Cyclin D
  • Cyclin E
  • Inostamycin
  • Phosphatidylinositol

ASJC Scopus subject areas

  • Biochemistry

Cite this

Inhibition of G1 cyclin expression in normal rat kidney cells by inostamycin, a phosphatidylinositol synthesis inhibitor. / Deguchi, Atsuko; Imoto, Masaya; Umezawa, Kazuo.

In: Journal of Biochemistry, Vol. 120, No. 6, 12.1996, p. 1118-1122.

Research output: Contribution to journalArticle

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