The VHL (von Hippel–Lindau) tumour-suppressor protein forms a multi-protein complex [VCB (pVHL–elongin C–elongin B)–Cul-2 (Cullin-2)] with elongin C, elongin B, Cul-2 and Rbx1, acting as a ubiquitin-ligase (E3) and directing proteasome-dependent degradation of targeted proteins. The α-subunit of Hif1α (hypoxia-inducible factor 1α) is the principal substrate for the VCB–Cul-2 complex; however, other substrates such as aPKC (atypical protein kinase C) have been reported. In the present study, we show with FRET (fluorescence resonance energy transfer) analysis measured by FLIM (fluorescence lifetime imaging microscopy) that PKCδ and pVHL (VHL protein) interact directly in cells. This occurs through the catalytic domain of PKCδ (residues 432–508), which appears to interact with two regions of pVHL, residues 113–122 and 130–154. Despite this robust interaction, analysis of the PMA-induced proteasome-dependent degradation of PKCδ in different RCC (renal cell carcinoma) lines (RCC4, UMRC2 and 786 O) shows that there is no correlation between the degradation of PKCδ and the presence of active pVHL. Thus, in contrast with aPKC, PKCδ is not a conventional substrate of the ubiquitin-ligase complex, VCB–Cul-2, and the observed interaction between these two proteins must underlie a distinct signalling output.
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Research Article|
June 14 2006
The von Hippel–Lindau tumour-suppressor protein interaction with protein kinase Cδ
Xavier Iturrioz;
Xavier Iturrioz
1
*Protein Phosphorylation Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London, WC2A 3PX, U.K.
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Joanne Durgan;
Joanne Durgan
*Protein Phosphorylation Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London, WC2A 3PX, U.K.
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Véronique Calleja;
Véronique Calleja
‡Cell Biophysics Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London, WC2A 3PX, U.K.
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Banafshé Larijani;
Banafshé Larijani
‡Cell Biophysics Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London, WC2A 3PX, U.K.
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Heiwa Okuda;
Heiwa Okuda
§Department of Urology, Kochi Medical School, Kochi 783-8505, Japan
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Richard Whelan;
Richard Whelan
*Protein Phosphorylation Laboratory, Cancer Research UK London Research Institute, 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 Research Institute, 44 Lincoln's Inn Fields, London, WC2A 3PX, U.K.
2To whom correspondence should be addressed (email peter.parker@cancer.org.uk).
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Publisher: Portland Press Ltd
Received:
March 06 2006
Revision Received:
April 25 2006
Accepted:
May 02 2006
Accepted Manuscript online:
May 02 2006
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2006
Biochem J (2006) 397 (1): 109–120.
Article history
Received:
March 06 2006
Revision Received:
April 25 2006
Accepted:
May 02 2006
Accepted Manuscript online:
May 02 2006
Citation
Xavier Iturrioz, Joanne Durgan, Véronique Calleja, Banafshé Larijani, Heiwa Okuda, Richard Whelan, Peter J. Parker; The von Hippel–Lindau tumour-suppressor protein interaction with protein kinase Cδ. Biochem J 1 July 2006; 397 (1): 109–120. doi: https://doi.org/10.1042/BJ20060354
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