Bombesin induces the down-regulation of protein kinase C-Δ (PKC-Δ) and PKC-ϵ in Swiss 3T3 cells. Simultaneous addition of transforming growth factor β1 (TGFβ1) selectively blocks PKC-Δ down-regulation at mid-S-phase, whereas PKC-ϵ levels continue to decline. Northern blot analysis shows that PKC-ϵ levels could be controlled in part at the level of transcription; PKC-Δ mRNA levels remained constant at these later times. Bombesin induces a sustained elevation of some species of diacylglycerol (DAG), consistent with the observed loss of PKC-Δ and PKC-ϵ. Interestingly, the combination of bombesin and TGF-β1 produces an even greater DAG response. Flow cytometric analysis demonstrates that bombesin induces only 15% of the cells to enter the cell cycle, in contrast to the combination of TGFβ1 plus bombesin which induces 75–80% of the cells to progress through the cycle. The protection of PKC-Δ from down-regulation under conditions of sustained DAG elevation correlates with the mitogenic response and implies that the down-regulation process itself is regulated. Consistent with this, it is demonstrated that bombesin plus TGFβ1 protects PKC-Δ from phorbol ester-induced down-regulation.
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Research Article|
September 01 1996
The co-mitogenic combination of transforming growth factor β1 and bombesin protects protein kinase C-δ from late-phase down-regulation, despite synergy in diacylglycerol accumulation
Andrée R. OLIVIER;
Andrée R. OLIVIER
‡
*Protein Phosphorylation Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London WC2A 3PX, U.K.
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Gurdip HANSRA;
Gurdip HANSRA
*Protein Phosphorylation Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London WC2A 3PX, U.K.
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Trevor R. PETTITT;
Trevor R. PETTITT
†Institute of Cancer Studies, University of Birmingham, Birmingham B15 2TT, U.K.
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Michael J. O. WAKELAM;
Michael J. O. WAKELAM
†Institute of Cancer Studies, University of Birmingham, Birmingham B15 2TT, U.K.
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Peter J. PARKER
Peter J. PARKER
§
*Protein Phosphorylation Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London WC2A 3PX, U.K.
§To whom correspondence should be addressed.
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Publisher: Portland Press Ltd
Received:
December 05 1995
Revision Received:
April 18 1996
Accepted:
May 08 1996
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1996
1996
Biochem J (1996) 318 (2): 519–525.
Article history
Received:
December 05 1995
Revision Received:
April 18 1996
Accepted:
May 08 1996
Citation
Andrée R. OLIVIER, Gurdip HANSRA, Trevor R. PETTITT, Michael J. O. WAKELAM, Peter J. PARKER; The co-mitogenic combination of transforming growth factor β1 and bombesin protects protein kinase C-δ from late-phase down-regulation, despite synergy in diacylglycerol accumulation. Biochem J 1 September 1996; 318 (2): 519–525. doi: https://doi.org/10.1042/bj3180519
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