Protein kinase D displays intrinsic Tyr autophosphorylation activity: insights into mechanism and regulation
journal contributionposted on 2020-07-15, 10:46 authored by Mathias Cobbaut, Rita Derua, Peter J Parker, Etienne Waelkens, Veerle Janssens, Johan Van Lint
The protein kinase D (PKD) family is regulated through multi-site phosphorylation, including autophosphorylation. For example, PKD displays in vivo autophosphorylation on Ser-742 (and Ser-738 in vitro) in the activation loop and Ser-910 in the C-tail (hPKD1 numbering). In this paper, we describe the surprising observation that PKD also displays in vitro autocatalytic activity towards a Tyr residue in the P + 1 loop of the activation segment. We define the molecular determinants for this unusual activity and identify a Cys residue (C705 in PKD1) in the catalytic loop as of utmost importance. In cells, PKD Tyr autophosphorylation is suppressed through the association of an inhibitory factor. Our findings provide important novel insights into PKD (auto)regulation.
autophosphorylationdual-specificitykinaseprotein kinase DAmino Acid SequenceAnimalsCOS CellsCells, CulturedChlorocebus aethiopsDrosophilaEnzyme ActivationHEK293 CellsHomeostasisHumansMutagenesis, Site-DirectedPhosphorylationProtein Kinase CTyrosineCercopithecus aethiopsParker FC0011300601 Biochemistry and Cell Biology0304 Medicinal and Biomolecular Chemistry0603 Evolutionary BiologyBiochemistry & Molecular Biology