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[Cancer Research 55, 774-780, February 15, 1995]
© 1995 American Association for Cancer Research

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Translocation of Protein Phosphatase 1 Catalytic Subunits during 1,25-Dihydroxyvitamin D3-induced Monocytic Differentiation of HL-60 Cells1

Serdar B. Omay, Hitoshi Ogasawara, Hideki Toyoda, Keiji Nakai, Hiroshi Shima, Minako Nagao, Marc C. Mumby, Hiroshi Shiku and Masakatsu Nishikawa2

The 2nd Department of Internal Medicine, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie 514, Japan [S. B. O., H. O., H. T., K. N., H. S., M. N.]; Carcinogenesis Division, National Cancer Research Institute, Tokyo, Japan [H. S., M. N.]; and Department of Pharmacology, University of Texas, Southwestern Medical Center, Dallas, Texas 75235-9041 [M. C. M.]

To elucidate the roles of protein phosphatases type 1 (PP1) and type 2A (PP2A) in 1,25-dihydroxy-cholecalciferol [1,25(OH)2D3]-induced differentiation of HL-60 cells into monocytes, we examined the enzyme activity and the protein and gene expressions of PP1 and PP2A in these cells. Calyculin-A augmented the 1,25(OH)2D3-induced differentiation of the cells. Treatment of the cells with 1,25(OH)2D3 led to a decrease in PP1-like activity in the cytosol fraction, with a concomitant increase in the membrane and nuclear PP1-like activity, as determined when protein phosphatase activity was assayed using myosin light chain as substrate in the presence of 5 nM okadaic acid. Western blot analysis with antibodies specific for PP1 catalytic subunit isozymes (PP1{alpha}, PP1{gamma}, and PP1{delta}) showed that all three PP1 isozymes were expressed but were differentially distributed in each cellular fraction. Subcellular redistribution of PP1-like activity during 1,25(OH)2D3-induced differentiation was mainly attributed to PP1{gamma} and PP1{alpha} proteins. In contrast, the localizations of PP1{delta} and PP2A catalytic and regulatory subunits were not significantly affected by 1,25(OH)2D3 treatment. The gene expressions of PP1{alpha} and PP1{gamma} appeared to be constant during processes of monocytic differentiation. The correlation between phenotypic and functional changes of HL-60 cells on the one hand and subcellular redistribution of PP1-like activity on the other suggest that the translocations of PP1{alpha} and PP1{gamma} isozymes may contribute to the 1,25(OH)2D3-induced monocytic differentiation of HL-60 cells.

1 This work was supported in part by grants for research from the Ministry of Education, Science and Culture of Japan.

2 To whom requests for reprints should be addressed.

Received 9/26/94. Accepted 12/ 9/94.




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
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Molecular Cancer Research Cancer Prevention Research
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Annual Meeting Education Book Meeting Abstracts Online
Copyright © 1995 by the American Association for Cancer Research.