PKCδ (protein kinase Cδ) is a serine/threonine kinase that plays a key role in growth regulation and tissue remodelling. Traditional models of PKC activation have focused on lipid cofactors and anchoring proteins that localize the active conformation of PKCδ to membranes, in close proximity with its target substrates. However, recent studies identify a distinct mode for PKCδ activation involving tyrosine phosphorylation by Src family kinases. The tyrosine-phosphorylated form of PKCδ (which accumulates in the soluble fraction of cells exposed to oxidant stress) displays lipid-independent kinase activity and is uniquely positioned to phosphorylate target substrates throughout the cell (not just on lipid membranes). This review summarizes (1) recent progress towards understanding structure–activity relationships for PKCδ, with a particular focus on the stimuli that induce (and the distinct functional consequences that result from) tyrosine phosphorylation events in PKCδ's regulatory, hinge and catalytic domains; (2) current concepts regarding the role of tyrosine phosphorylation as a mechanism to regulate PKCδ localization and actions in mitochondrial and nuclear compartments; and (3) recent literature delineating distinct roles for PKCδ (relative to other PKC isoforms) in transcriptional regulation, cell cycle progression and programmed cell death (including studies in PKCδ−/− mice that implicate PKCδ in immune function and cardiovascular remodelling). Collectively, these studies argue that the conventional model for PKCδ activation must be broadened to allow for stimulus-specific differences in PKCδ signalling during growth factor stimulation and oxidant stress.
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December 2004
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Review Article|
December 07 2004
Distinctive activation mechanisms and functions for protein kinase Cδ
Susan F. STEINBERG
Susan F. STEINBERG
1
1Department of Pharmacology, College of Physicians and Surgeons, Columbia University, 630 West 168 Street, New York, NY 10032, U.S.A.
1email sfs1@columbia.edu
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Biochem J (2004) 384 (3): 449–459.
Article history
Received:
April 29 2004
Revision Received:
August 26 2004
Accepted:
October 19 2004
Accepted Manuscript online:
October 19 2004
Citation
Susan F. STEINBERG; Distinctive activation mechanisms and functions for protein kinase Cδ. Biochem J 15 December 2004; 384 (3): 449–459. doi: https://doi.org/10.1042/BJ20040704
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