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The V5 domain of pr...
The V5 domain of protein kinase C plays a critical role in determining the isoform-specific localization, translocation, and biological function of protein kinase C-delta and -epsilon
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Wang, QMJ (författare)
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Lu, GW (författare)
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Schlapkohl, WA (författare)
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Goerke, A (författare)
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- Larsson, Christer (författare)
- Lund University,Lunds universitet,Institutionen för translationell medicin,Medicinska fakulteten,Department of Translational Medicine,Faculty of Medicine
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Mischak, H (författare)
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Blumberg, PM (författare)
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Mushinski, JF (författare)
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(creator_code:org_t)
- 2004
- 2004
- Engelska.
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Ingår i: Molecular Cancer Research. - 1557-3125. ; 2:2, s. 129-140
- Relaterad länk:
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http://mcr.aacrjourn...
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https://lup.lub.lu.s...
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Abstract
Ämnesord
Stäng
- The catalytic domain of overexpressed protein kinase C (PKC)-delta mediates phorbol 12-myristate 13-acetate (PMA)-induced differentiation or apoptosis in appropriate model cell lines. To define the portions of the catalytic domain that are critical for these isozyme-specific functions, we constructed reciprocal chimeras, PKC-delta/epsilonV5 and -epsilon/deltaV5, by swapping the V5 domains of PKC-delta and -epsilon. PKC-delta/epsilonV5 failed to mediate PMA-induced differentiation of 32D cells, showing the essential nature of the V5 domain for PKC-delta's functionality. The other chimera, PKC-epsilon/deltaV5, endowed inactive PKC-epsilon with nearly all PKC-delta's apoptotic ability, confirming the importance of PKC-delta in this function. Green fluorescent protein (GFP)-tagged PKC-deltaV5 and -epsilon/deltaV5 in A7r5 cells showed substantial basal nuclear localization, while GFP-tagged PKC-epsilon and -delta/epsilonV5 showed significantly less, indicating that the V5 region of PKC-delta contains determinants critical to its nuclear distribution. PKC-epsilon/deltaV5-GFP showed much slower kinetics of translocation to membranes in response to PMA than parental PKC-epsilon, implicating the PKC-epsilonV5 domain in membrane targeting. Thus, the V5 domain is critical in several of the isozyme-specific functions of PKC-delta and -epsilon.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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