Dominant negative properties are conferred on protein kinase (PK) Cα by mutation of the phosphorylation site in the activation loop of the kinase domain. To address the universality and/or specificity of such mutations, analogous alterations were introduced in other members of the PKC family and tested for their effects on the function of co-transfected activated PKC. For all three subclasses of the PKC family, mutations of the predicted activation loop phosphorylation sites resulted in dominant negative properties. These properties were not restricted to the cognate PKC isotypes, but were effective across the different subclasses. For example, two PKCζ mutants (atypical isotype) inhibited both PKCα (classical isotype) and PKCε (novel isotype). For all these mutants, inhibition correlated with an ability to prevent the accumulation of phosphorylated PKCα, consistent with the expected mode of action. In the case of the PKCα mutant, it was shown that inhibition required the full-length mutant protein. The results provide evidence for the involvement of a common step in the phosphorylation of all PKC isotypes.
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August 1998
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Research Article|
August 01 1998
The broad specificity of dominant inhibitory protein kinase C mutants infers a common step in phosphorylation
Pilar GARCIA-PARAMIO;
Pilar GARCIA-PARAMIO
1Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London WC2A 3PX, U.K.
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Yolanda CABRERIZO;
Yolanda CABRERIZO
1Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London WC2A 3PX, U.K.
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Frederic BORNANCIN;
Frederic BORNANCIN
1
1Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London WC2A 3PX, U.K.
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Peter J. PARKER
Peter J. PARKER
2
1Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London WC2A 3PX, U.K.
2To whom correspondence should be addressed.
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Publisher: Portland Press Ltd
Received:
December 16 1997
Revision Received:
April 20 1998
Accepted:
April 28 1998
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1998
1998
Biochem J (1998) 333 (3): 631–636.
Article history
Received:
December 16 1997
Revision Received:
April 20 1998
Accepted:
April 28 1998
Citation
Pilar GARCIA-PARAMIO, Yolanda CABRERIZO, Frederic BORNANCIN, Peter J. PARKER; The broad specificity of dominant inhibitory protein kinase C mutants infers a common step in phosphorylation. Biochem J 1 August 1998; 333 (3): 631–636. doi: https://doi.org/10.1042/bj3330631
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