caa a22 4500 397555709 CHVBK 20180308164801.0 cr unu---uuuuu 161202e199612 xx s 000 0 eng 10.1093/oxfordjournals.jbchem.a021530 doi (NATIONALLICENCE)oxford-10.1093/oxfordjournals.jbchem.a021530 Inhibition of G1 Cyclin Expression in Normal Rat Kidney Cells by Inostamycin, a Phosphatidylinositol Synthesis Inhibitor [Elektronische Daten] [Atsuko Deguchi, Masaya Imoto, Kazuo Umezawa] 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 mm 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 Dl and E expressions. © 1996 BY THE JOURNAL OF BIOCHEMISTRY Regular Papers nationallicence cdk2 nationallicence cyclin D nationallicence cyclin E nationallicence inostamycin nationallicence phosphatidylinositol nationallicence Deguchi Atsuko Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223 aut Imoto Masaya Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223 aut Umezawa Kazuo Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223 aut The Journal of Biochemistry Oxford University Press 120/6(1996-12), 1118-1122 0021-924X 120:6<1118 1996 120 jbchem https://doi.org/10.1093/oxfordjournals.jbchem.a021530 text/html Onlinezugriff via DOI 1 other jats NATIONALLICENCE 856 40 https://doi.org/10.1093/oxfordjournals.jbchem.a021530 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Deguchi Atsuko Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223 aut NATIONALLICENCE 700 1- Imoto Masaya Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223 aut NATIONALLICENCE 700 1- Umezawa Kazuo Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223 aut NATIONALLICENCE 773 0- The Journal of Biochemistry Oxford University Press 120/6(1996-12), 1118-1122 0021-924X 120:6<1118 1996 120 jbchem Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford