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Functional association of TGF-β receptor II with cyclin B

Oncogene volume 18, pages 269–275 (1999)Cite this article

Abstract

Utilizing the cytoplasmic tail of Transforming Growth Factor Receptor Type II (TGFβ RII) as bait in a yeast two hybrid system, we have identified human cyclin B2 as a direct physical partner of TGFβ RII. Analysis of deletion mutants of glutathione-S-transferase (GST)-cyclin B2 mapped its binding domain for TGFβ RII to the C-terminal and revealed a negative regulatory region immediately upstream of the cyclin box. Using recombinant proteins, Cdc2 was demonstrated to indirectly interact with TGFβ RII via cyclin B2. This interaction was reproduced in THP-1 monocytic cells, where TGFβ treatment markedly enhanced the ability of cyclin B2 and, correspondingly, Cdc2 from TGFβ-treated THP-l cells, to bind the GST-TGFβ RII fusion protein. More importantly, TGFβ RII co-precipitated with cyclin B2 in TGFβ-treated THP-1 cells. TGFβ treatment also caused threonine phosphorylation of Cdc2 in the TGFβ RII-cyclin B2-Cdc2 complex in THP1 cells, in parallel with down regulation of Cdc2 function as measured by histone H1 kinase activity. Cyclin B1 had the same capacity to bind TGFβ RII and mediate indirect Cdc2 binding. These results suggest an alternative mechanism that cell cycle arrest in the G1/S phase caused by TGFβ may, in part, be due to inactivation of cyclin B/Cdc2 kinase, which is needed for entry into the G2/M phase.

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Acknowledgements

We are grateful to Dr X-F Wang (Duke University Medical Center, Durham, NC, USA) for the TGFβ receptor type II plasmid, Dr Steven I Reed (Scripps Research Institute, La Jolla, CA, USA) for full length cyclin B2, and Dr Tony Hunter (The Salk Institute for Biological Studies, San Diego, CA, USA) for cyclin B1 and Cdc2 plasmids.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Immunology Program, H Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, 33612, Florida, USA

    Jin Hong Liu, Sheng Wei, Pearlie K Burnette, Ana M Gamero & Julie Y Djeu

  2. Mayo Clinic, Jacksonville, Florida, USA

    Michael Hutton

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  1. Jin Hong Liu
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Liu, J., Wei, S., Burnette, P. et al. Functional association of TGF-β receptor II with cyclin B. Oncogene 18, 269–275 (1999). https://doi.org/10.1038/sj.onc.1202263

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