The tumour-associated D294G mutant of protein kinase Cα (PKCα) was recently shown not to be translocated to the plasma membrane on stimulation with PMA, in contrast with the wild-type enzyme. Using recombinant wild-type and mutant PKCα, we establish here that, although the PKCα intrinsic lipid-dependent catalytic activity remains unaltered by the D294G mutation, the mutant enzyme exhibits a selective loss of substrate recognition. Indeed, whereas the mutant enzyme is still able to phosphorylate histone IIIS with comparable efficiency to that of the wild-type enzyme, it exhibits a lack of kinase activity towards the previously cloned 35F and 35H substrates for PKC. Overlay experiments demonstrate that this selective loss of kinase activity is correlated with a decrease in binding of D294G PKCα to the 35F and 35H proteins compared with that of the wild-type enzyme. Because the 35H and 35F proteins are predicted to be PKCα-anchoring proteins, these findings suggest a selective loss of PKCα–protein interactions that might fail to stabilize the location of the PKCα mutant at the plasma membrane.
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September 1998
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Research Article|
September 01 1998
Selective loss of substrate recognition induced by the tumour-associated D294G point mutation in protein kinase Cα
Corinne PRÉVOSTEL;
Corinne PRÉVOSTEL
*INSERM U469, 141 rue de la Cardonille, 34094 Montpellier cedex 05, France
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Véronique ALVARO;
Véronique ALVARO
†Centre d'Études du Polymorphisme Humain, Fondation J. Dausset, 27 rue Juliette Dodu, 75010 Paris, France
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Alice VALLENTIN;
Alice VALLENTIN
*INSERM U469, 141 rue de la Cardonille, 34094 Montpellier cedex 05, France
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Annick MARTIN;
Annick MARTIN
*INSERM U469, 141 rue de la Cardonille, 34094 Montpellier cedex 05, France
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Susan JAKEN;
Susan JAKEN
‡W. Alton Jones Cell Science Center, Lake Placid, NY 12946, U.S.A.
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Dominique JOUBERT
Dominique JOUBERT
1
*INSERM U469, 141 rue de la Cardonille, 34094 Montpellier cedex 05, France
1To whom correspondence should be addressed (e-mail joubert@u469.montp.inserm.fr).
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Publisher: Portland Press Ltd
Revision Received:
May 20 1998
Accepted:
June 26 1998
Received:
December 19 1998
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1998
1998
Biochem J (1998) 334 (2): 393–397.
Article history
Revision Received:
May 20 1998
Accepted:
June 26 1998
Received:
December 19 1998
Citation
Corinne PRÉVOSTEL, Véronique ALVARO, Alice VALLENTIN, Annick MARTIN, Susan JAKEN, Dominique JOUBERT; Selective loss of substrate recognition induced by the tumour-associated D294G point mutation in protein kinase Cα. Biochem J 1 September 1998; 334 (2): 393–397. doi: https://doi.org/10.1042/bj3340393
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