Classical and novel protein kinase C (PKC) isoforms are down-regulated as a result of chronic activation by certain tumour promoters and physiological stimuli; however, the mechanisms leading to down-regulation are not fully understood. In the present study, we have studied the PMA ('TPA')-induced degradation of PKCΔ in NIH 3T3 cells under culture conditions where PKCΔ displays cell-cycle-dependent down-regulation. In contrast with previous studies, a hyperphosphorylated form of this PKC isoform, promoted by calyculin A, was rapidly degraded in PMA-treated cells. Similarly, the presence of calyculin A enhanced the down-regulation of PKCΔ observed on G1/S-phase progression through the cell cycle. Analysis of phosphorylation-site mutants indicated that the T-loop Thr505 phosphorylation site was critical for induced degradation.
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November 2002
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Research Article|
November 15 2002
Phosphorylation is required for PMA- and cell-cycle-induced degradation of protein kinase Cδ
Jyoti SRIVASTAVA;
Jyoti SRIVASTAVA
1
Protein Phosphorylation Laboratory, Cancer Research UK London Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, U.K.
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Katarzyna J. PROCYK;
Katarzyna J. PROCYK
Protein Phosphorylation Laboratory, Cancer Research UK London Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, U.K.
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Xavier ITURRIOZ;
Xavier ITURRIOZ
Protein Phosphorylation Laboratory, Cancer Research UK London Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, U.K.
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Peter J. PARKER
Peter J. PARKER
2
Protein Phosphorylation Laboratory, Cancer Research UK London Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, U.K.
2To whom correspondence should be addressed (e-mail peter.parker@cancer.org.uk).
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Publisher: Portland Press Ltd
Received:
May 10 2002
Revision Received:
August 19 2002
Accepted:
September 04 2002
Accepted Manuscript online:
September 04 2002
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2002
2002
Biochem J (2002) 368 (1): 349–355.
Article history
Received:
May 10 2002
Revision Received:
August 19 2002
Accepted:
September 04 2002
Accepted Manuscript online:
September 04 2002
Citation
Jyoti SRIVASTAVA, Katarzyna J. PROCYK, Xavier ITURRIOZ, Peter J. PARKER; Phosphorylation is required for PMA- and cell-cycle-induced degradation of protein kinase Cδ. Biochem J 15 November 2002; 368 (1): 349–355. doi: https://doi.org/10.1042/bj20020737
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