ArticleThe Journal of biological chemistry2011
Involvement of protein kinase D in expression and trafficking of ATP7B (copper ATPase).
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 43 citations in OpenAlex.
- Balancing cellular copper levels via the post-translational regulation of copper transport.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Review
- Electrospun nanofiber scaffolds loaded with copper oxide for repairing traumatic brain injury through restoring copper homeostasis and regulating pyroptosis pathway.Burns & trauma · 2025Article
- Hepatolenticular degeneration-induced hepatic dysfunction with extremely atypical clinical manifestations: a Case Report.Frontiers in medicine · 2025Article
- Dynamic and cell-specific transport networks for intracellular copper ions.Journal of cell science · 2021Review
- Single nucleotide polymorphisms in the human ATP7B gene modify the properties of the ATP7B protein.Metallomics : integrated biometal science · 2019Article
- ATP7A and ATP7B copper transporters have distinct functions in the regulation of neuronal dopamine-β-hydroxylase.The Journal of biological chemistry · 2018Article
- Modulating Chemosensitivity of Tumors to Platinum-Based Antitumor Drugs by Transcriptional Regulation of Copper Homeostasis.International journal of molecular sciences · 2018Review
- Akt2 (Protein Kinase B Beta) Stabilizes ATP7A, a Copper Transporter for Extracellular Superoxide Dismutase, in Vascular Smooth Muscle: Novel Mechanism to Limit Endothelial Dysfunction in Type 2 Diabetes Mellitus.Arteriosclerosis, thrombosis, and vascular biology · 2018Article
- The six metal binding domains in human copper transporter, ATP7B: molecular biophysics and disease-causing mutations.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2017Review
- The metal chaperone Atox1 regulates the activity of the human copper transporter ATP7B by modulating domain dynamics.The Journal of biological chemistry · 2017Article
- Copper trafficking to the secretory pathway.Metallomics : integrated biometal science · 2016Review
- Communication between the N and C termini is required for copper-stimulated Ser/Thr phosphorylation of Cu(I)-ATPase (ATP7B).The Journal of biological chemistry · 2015Article
- Interactions between metal-binding domains modulate intracellular targeting of Cu(I)-ATPase ATP7B, as revealed by nanobody binding.The Journal of biological chemistry · 2014Article
- Biochemical characterization of P-type copper ATPases.The Biochemical journal · 2014Review
- Golgi in copper homeostasis: a view from the membrane trafficking field.Histochemistry and cell biology · 2013Review
- Molecular events initiating exit of a copper-transporting ATPase ATP7B from the trans-Golgi network.The Journal of biological chemistry · 2012Article
- Distinctive features of catalytic and transport mechanisms in mammalian sarco-endoplasmic reticulum Ca2+ ATPase (SERCA) and Cu+ (ATP7A/B) ATPases.The Journal of biological chemistry · 2012Article
- Dynamic multibody protein interactions suggest versatile pathways for copper trafficking.Journal of the American Chemical Society · 2012Article
- Regulation of copper transporters in human cells.Current topics in membranes · 2012Review
- Calcium and copper transport ATPases: analogies and diversities in transduction and signaling mechanisms.Journal of cell communication and signaling · 2011Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
ATP7B is a P-type ATPase involved in copper transport and homeostasis. In experiments with microsomes isolated from COS-1 cells or HepG2 hepatocytes sustaining ATP7B heterologous expression, we found that ATP7B utilization of ATP includes autophosphorylation of an aspartyl residue serving as ATPase catalytic intermediate as well as phosphorylation of serine residues by protein kinase D (PKD). The latter was abolished by specific PKD inhibition with CID755673. The presence of PKD protein in the microsomal fraction was demonstrated by Western blotting. PKD is a serine/threonine kinase that associates with the trans-Golgi network, regulating fission of transport carriers destined to the cell surface. Parallel studies on cultured cells showed that nascent WT ATP7B transits to the Golgi complex where it undergoes serine phosphorylation by PKD. Misfolded ATP7B protein (especially if subjected to deletions) underwent proteasome-mediated degradation, which provides effective quality control. Inhibition of proteasome-mediated degradation with MG132 yielded additional, but nonfunctional protein. On the other hand, serine phosphorylation protected WT ATP7B from degradation. Protection was enhanced by PKD activation with phorbol esters and limited by PKD inhibition with CID75673. As a final step, phosphorylated ATP7B was transferred from the Golgi complex to cytosolic trafficking vesicles. Phosphorylation and trafficking were completely prevented by mutations of critical copper binding sites, demonstrating copper dependence of both PKD-assisted phosphorylation and trafficking. ATP7B trafficking was markedly reduced by the Ser-478/481/1121/1453 to Ala mutation. We conclude that PKD plays a key role in copper-dependent serine phosphorylation, permitting high levels of ATP7B protein expression and trafficking.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.