Protein kinase D activation by deletion of its cysteine-rich motifs

Protein kinase D is a serine/threonine kinase that binds phorbol esters in a phospholipid-dependent manner via a tandemly repeated cysteine-rich, zinc finger-like motif (the cysteine-rich domain). Here, we examined whether the cysteine-rich domain plays an additional role in the control of the catalytic kinase activity independently of the binding of allosteric effectors. We found that deletion of cys1, cys2 or the entire cysteine-rich domain increases the basal activity of protein kinase D leading to a constitutively active form of this enzyme. Our results demonstrate, for the first time, that the cysteine-rich domain of Protein kinase D plays a negative role in the regulation of protein kinase D kinase activity.