A novel tyrosine phosphorylation site in protein kinase D contributes to oxidative stress-mediated activation

Heike Döppler, Peter Storz

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Protein kinase D1 (PKD1) is a mediator of oxidative stress signaling where it regulates cellular detoxification and survival. Critical for the regulation of PKD1 activity in response to oxidative stress are Src- and Abl-mediated tyrosine phosphorylations that eventually lead to protein kinase Cδ(PKCδ)-mediated activation of PKD1. Here we identify Tyr 95 in PKD1 as a previously undescribed phosphorylation site that is regulated by oxidative stress. Our data suggest that PKD1 phosphorylation at Tyr95 generates a binding motif for PKCδ, and that oxidative stress-mediated PKCδ/PKD interaction results in PKD1 activation loop phosphorylation and activation. We further analyzed all PKD isoforms for this mechanism and show that PKD enzymes PKD1 and PKD2 are targets for PKCδ in response to oxidative stress, and that PKD3 is not a target because it lacks the relevant tyrosine residue that generates a PKCδ interaction motif.

Original languageEnglish (US)
Pages (from-to)31873-31881
Number of pages9
JournalJournal of Biological Chemistry
Volume282
Issue number44
DOIs
StatePublished - Nov 2 2007

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Phosphorylation
Oxidative stress
Protein Kinases
Tyrosine
Oxidative Stress
Chemical activation
Protein Kinase C
Detoxification
Heat-Shock Proteins
protein kinase D
Carrier Proteins
Protein Isoforms
Enzymes

ASJC Scopus subject areas

  • Biochemistry

Cite this

A novel tyrosine phosphorylation site in protein kinase D contributes to oxidative stress-mediated activation. / Döppler, Heike; Storz, Peter.

In: Journal of Biological Chemistry, Vol. 282, No. 44, 02.11.2007, p. 31873-31881.

Research output: Contribution to journalArticle

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