Protein kinase D activation by mutations within its pleckstrin homology domain.

The Journal of Biological Chemistry
T Iglesias, Enrique Rozengurt

Abstract

Protein kinase D (PKD) is a serine/threonine protein kinase that contains a cysteine-rich repeat sequence homologous to that seen in the regulatory domain of protein kinase C (PKC) and a catalytic domain with only a low degree of sequence similarity to PKCs. PKD also contains a pleckstrin homology (PH) domain inserted between the cysteine-rich motifs and the catalytic domain that is not present in any of the PKCs. To investigate the function of the PH domain in the regulation of PKD activity, we determined the kinase activity of several PKD PH domain mutants immunoprecipitated from lysates of transiently transfected COS-7 cells. Deletion of the entire PH domain (amino acids 429-557) markedly increased the basal activity of the enzyme as assessed by autophosphorylation ( approximately 16-fold) and exogenous syntide-2 peptide substrate phosphorylation assays (approximately 12-fold). Mutant PKD proteins with partial deletions or single amino acid substitutions within the PH domain (e. g. R447C and W538A) also exhibited increased basal kinase activity. These constitutive active mutants of PKD were only slightly further stimulated by phorbol-12,13-dibutyrate treatment of intact cells. Our results demonstrate, for the first time, tha...Continue Reading

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Citations

Aug 6, 2009·Molecules and Cells·Chang Hoon Ha, Zheng Gen Jin
Mar 21, 2003·Biochemical and Biophysical Research Communications·Osvaldo ReyEnrique Rozengurt
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