Selective loss of substrate recognition induced by the tumour-associated D294G point mutation in protein kinase Cα

被引:11
作者
Prévostel, C
Alvaro, V
Vallentin, A
Martin, A
Jaken, S
Joubert, D
机构
[1] INSERM, U469, F-34094 Montpellier 05, France
[2] Fdn J Dausset, Ctr Etud Polymorphisme Humain, F-75010 Paris, France
[3] W Alton Jones Cell Sci Ctr, Lake Placid, NY 12946 USA
关键词
D O I
10.1042/bj3340393
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The tumour-associated D294G mutant of protein kinase C alpha (PKC alpha) was recently shown not to be translocated to the plasma membrane on stimulation with PMA, in contrast with the wildtype enzyme. Using recombinant wild-type and mutant PKC alpha, we establish here that, although the PKC alpha 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 PKC alpha to the 35F and 35H proteins compared with that of the wild-type enzyme. Because the 35H and 35F proteins are predicted to be PKC alpha-anchoring proteins, these findings suggest a selective loss of PKC alpha-protein interactions that might fail to stabilize the location of the PKC alpha mutant at the plasma membrane.
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页码:393 / 397
页数:5
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