Protein Kinase D Displays Intrinsic Tyr Autophosphorylation Activity: Insights into Mechanism and Regulation

Overview

Journal FEBS Lett

Specialty Biochemistry

Date 2018 Jun 23

PMID 29933512

Citations 2

Authors

Mathias Cobbaut

Rita Derua

Peter J Parker

Etienne Waelkens

Veerle Janssens

Johan Van Lint

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

A critical evaluation of protein kinase regulation by activation loop autophosphorylation.

Reinhardt R, Leonard T Elife. 2023; 12.

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Control of atypical PKCι membrane dissociation by tyrosine phosphorylation within a PB1-C1 interdomain interface.

Cobbaut M, McDonald N, Parker P J Biol Chem. 2023; 299(7):104847.

PMID: 37211093 PMC: 10333572. DOI: 10.1016/j.jbc.2023.104847.

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