Protein kinase D displays intrinsic Tyr autophosphorylation activity: insights into mechanism and regulation

Mathias Cobbaut; Rita Derua; Peter J. Parker; Etienne Waelkens; Veerle Janssens; Johan Van Lint

doi:10.1002/1873-3468.13171

Protein kinase D displays intrinsic Tyr autophosphorylation activity: insights into mechanism and regulation

Mathias Cobbaut, Rita Derua, Peter J. Parker, Etienne Waelkens, Veerle Janssens, Johan Van Lint^*

^*Corresponding author for this work

Institute of Psychiatry, Psychology & Neuroscience

Research output: Contribution to journal › Article › peer-review

4 Citations (Scopus)

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.

Original language	English
Pages (from-to)	2432-2443
Number of pages	12
Journal	FEBS Letters
Volume	592
Issue number	14
DOIs	https://doi.org/10.1002/1873-3468.13171
Publication status	Published - 1 Jul 2018

Keywords

autophosphorylation
dual-specificity
kinase
protein kinase D

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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title = "Protein kinase D displays intrinsic Tyr autophosphorylation activity: insights into mechanism and regulation",

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.",

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T1 - Protein kinase D displays intrinsic Tyr autophosphorylation activity

T2 - insights into mechanism and regulation

AU - Cobbaut, Mathias

AU - Derua, Rita

AU - Parker, Peter J.

AU - Waelkens, Etienne

AU - Janssens, Veerle

AU - Van Lint, Johan

PY - 2018/7/1

Y1 - 2018/7/1

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AB - 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.

KW - autophosphorylation

KW - dual-specificity

KW - kinase

KW - protein kinase D

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Protein kinase D displays intrinsic Tyr autophosphorylation activity: insights into mechanism and regulation

Abstract

Keywords

UN SDGs

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