Protein Kinase C μ Is Negatively Regulated by 14-3-3 Signal Transduction Proteins

Haußer, Angelika; Störz, Peter; Link, Gisela; Stoll, Hartmut; Liu, Yun‐Cai; Altman, Amnon; Pfizenmaier, Klaus; Johannes, Franz Josef

doi:10.1074/jbc.274.14.9258

Cited by 103 publications

(104 citation statements)

References 44 publications

(65 reference statements)

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“…As a feasible explanation to the lack of endogenous PKD activity in the axon, we can assume that inactivation of PKD, e.g., via sequestration by 14-3-3 adapter proteins (Hausser et al, 1999;Taya et al, 2007) is selectively increased in the axons. At the same time, selective dephosphorylation of PKD, the reporter, or both (Uetani et al, 2006) has to be also taken into consideration.…”

Section: Discussionmentioning

confidence: 99%

“…Fluorescently tagged human wtPKD1-GFP, kdPKD1-GFP (PKC K612W -EGFP), PKD1⌬PH-GFP, or caPKD1-GFP (PKD1 S738/742E ) plasmids have been described previously (Hausser et al, 1999(Hausser et al, , 2002(Hausser et al, , 2005. pEGFP-C1, pEGFP-N1, and pmCherry-N1 vectors were from Clontech Europe (Saint-Germain-enLaye, France) and A. Jeromin, Allen Institute for Brain Science (Seattle, WA), respectively.…”

Section: Expression Constructsmentioning

confidence: 99%

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Protein Kinase D Controls the Integrity of Golgi Apparatus and the Maintenance of Dendritic Arborization in Hippocampal Neurons

Czöndör

Ellwanger²,

Fuchs³

et al. 2009

MBoC

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Protein kinase D (PKD) is known to participate in various cellular functions, including secretory vesicle fission from theGolgi and plasma membrane-directed transport. Here, we report on expression and function of PKD in hippocampal neurons. Expression of an enhanced green fluorescent protein (EGFP)-tagged PKD activity reporter in mouse embryonal hippocampal neurons revealed high endogenous PKD activity at the Golgi complex and in the dendrites, whereas PKD activity was excluded from the axon in parallel with axonal maturation. Expression of fluorescently tagged wild-type PKD1 and constitutively active PKD1 S738/742E (caPKD1) in neurons revealed that both proteins were slightly enriched at the trans-Golgi network (TGN) and did not interfere with its thread-like morphology. By contrast, expression of dominant-negative kinase inactive PKD1 K612W (kdPKD1) led to the disruption of the neuronal Golgi complex, with kdPKD1 strongly localized to the TGN fragments. Similar findings were obtained from transgenic mice with inducible, neuron-specific expression of kdPKD1-EGFP. As a prominent consequence of kdPKD1 expression, the dendritic tree of transfected neurons was reduced, whereas caPKD1 increased dendritic arborization. Our results thus provide direct evidence that PKD activity is selectively involved in the maintenance of dendritic arborization and Golgi structure of hippocampal neurons. INTRODUCTIONNeurons are nondividing and extremely polarized cells, with enormous membrane surface compared with the size of the soma. These features assume a highly specialized secretory machinery, which resembles in certain parts the directed transport mechanisms described in polarized nonneuronal cells (Winckler and Mellman, 1999;Horton and Ehlers, 2004). The vast neuronal membrane surface is functionally and structurally divided into axonal and somatodendritic compartments, possessing specific lipid and protein components required for the spatially different functions, e.g., for pre-or postsynaptic activity (Dresbach et al., 2001;Sheng, 2001;Bresler et al., 2004). The constitutive and precisely directed supply of surface membrane components is indispensable for the function of neurons, especially when considering that postmitotic neurons normally serve throughout the life span of the organism. Up to now, we are far from understanding how the extreme polarization has been evolved and is maintained in neurons.Despite a likely central role in neuronal morphogenesis and membrane trafficking, little is known about the special structure and transport features of the neuronal Golgi apparatus. A thread-like and reticular structure of the Golgi apparatus has been already described in many neuronal types (Takamine et al., 2000;Fujita and Okamoto, 2005;Horton et al., 2005). Central neuronal Golgi complex is localized in the soma and often extends into the principal dendrites, but Golgi elements were also found as discontinuous structures in the distal dendrites, often near synaptic contacts or in dendritic spines (Gardiol et al., 1999;Pierc...

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Section: Discussionmentioning

confidence: 99%

Section: Expression Constructsmentioning

confidence: 99%

Protein Kinase D Controls the Integrity of Golgi Apparatus and the Maintenance of Dendritic Arborization in Hippocampal Neurons

Czöndör

Ellwanger²,

Fuchs³

et al. 2009

MBoC

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“…It is therefore likely that the downstream effects of PKC⑀ are mediated by the C1 domains. These structures have in several studies been shown to exert different biological effects (Lehel et al, 1995;Pawelczyk et al, 1998;Kiss et al, 1999;Aroca et al, 2000) and to interact with other proteins (Matto-Yelin et al, 1997;Yao et al, 1997;Pawelczyk et al, 1998;Hausser et al, 1999;Johannes et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Protein Kinase Cε Actin-binding Site Is Important for Neurite Outgrowth during Neuronal Differentiation

Zeidman

Trollér

Raghunath

et al. 2002

MBoC

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We have previously shown that protein kinase C⑀ (PKC⑀) induces neurite outgrowth via its regulatory domain and independently of its kinase activity. This study aimed at identifying mechanisms regulating PKC⑀-mediated neurite induction. We show an increased association of PKC⑀ to the cytoskeleton during neuronal differentiation. Furthermore, neurite induction by overexpression of full-length PKC⑀ is suppressed if serum is removed from the cultures or if an actin-binding site is deleted from the protein. A peptide corresponding to the PKC⑀ actin-binding site suppresses neurite outgrowth during neuronal differentiation and outgrowth elicited by PKC⑀ overexpression. Neither serum removal, deletion of the actin-binding site, nor introduction of the peptide affects neurite induction by the isolated regulatory domain. Membrane targeting by myristoylation renders full-length PKC⑀ independent of both serum and the actin-binding site, and PKC⑀ colocalized with F-actin at the cortical cytoskeleton during neurite outgrowth. These results demonstrate that the actin-binding site is of importance for signals acting on PKC⑀ in a pathway leading to neurite outgrowth. Localization of PKC⑀ to the plasma membrane and/or the cortical cytoskeleton is conceivably important for its effect on neurite outgrowth.

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“…The N-terminal domain, and the zinc finger motifs in particular, appear to be important in regulating PKD subcellular localization [reviewed in (1)]. There is also a conserved serine autophosphorylation site between the zinc finger motifs that is required for interaction with 14-3-3 protein, whose binding negatively regulates PKD activity (2,3). In addition, the PKD1 regulatory domain possesses an alanine and proline rich apolar region in the N-terminus, whereas the PKD2 regulatory domain has a proline rich region, and also contains a serine-rich linker between the zinc finger motifs.…”

Section: Introductionmentioning

confidence: 99%

Protein kinase D in vascular biology and angiogenesis

Evans

Zachary

2011

IUBMB Life

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SummaryThe Protein Kinase D (PKD) family comprises diacylglycerol stimulated serine/threonine protein kinases that participate in many key signaling pathways in a diverse range of cells. Recent studies show that PKD isoforms 1 and 2 play critical roles in vascular biology and angiogenesis and there has been considerable progress in determining some of the key angiogenic signaling pathways mediated by PKD in endothelial cells. Less is currently known regarding the specific roles of PKD isoforms in endothelial cells and the role of PKD in smooth muscle cells. PKD is also emerging as a potentially important mediator of tumor growth and tumor angiogenesis and there is growing interest in PKD as a novel therapeutic target in cancer.

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Protein Kinase C μ Is Negatively Regulated by 14-3-3 Signal Transduction Proteins

Cited by 103 publications

References 44 publications

Protein Kinase D Controls the Integrity of Golgi Apparatus and the Maintenance of Dendritic Arborization in Hippocampal Neurons

Protein Kinase D Controls the Integrity of Golgi Apparatus and the Maintenance of Dendritic Arborization in Hippocampal Neurons

Protein Kinase Cε Actin-binding Site Is Important for Neurite Outgrowth during Neuronal Differentiation

Protein kinase D in vascular biology and angiogenesis

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