Functional association of TGF-β receptor II with cyclin B

Jin Hong Liu, Sheng Wei, Pearlie K. Burnette, Ana M. Gamero, Michael Hutton, Julie Y. Djeu

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

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-1 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.

Original languageEnglish
Pages (from-to)269-275
Number of pages7
JournalOncogene
Volume18
Issue number1
DOIs
StatePublished - Jan 7 1999

Keywords

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • CDC2 Protein Kinase/metabolism
  • Cell Line
  • Cell Line, Transformed
  • Cyclin B/genetics
  • Cyclin B1
  • Cyclin B2
  • Humans
  • Molecular Sequence Data
  • Phosphorylation
  • Protein Serine-Threonine Kinases
  • Rabbits
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta/genetics
  • Recombinant Fusion Proteins/genetics
  • Transforming Growth Factor beta/metabolism

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