ArticleAmerican journal of physiology. Renal physiology2014
Akt recruits Dab2 to albumin endocytosis in the proximal tubule.
Article in American journal of physiology. Renal physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- Linagliptin increases the expression of LRP2 independent of Nrf2 in streptozotocin-induced diabetic mice.Journal of diabetes investigation · 2026Article
- Tubulointerstitial inflammation and fibrosis induced by proteinuria: fresh insights.Frontiers in pharmacology · 2026Review
- Downregulation of Akt induces proximal tubule epithelial cell apoptosis via FOXO and BIM pathway in proteinuric States.Scientific reports · 2025Article
- Human Disabled-2 regulates thromboxane ANature communications · 2024Article
- Albumin Nanoparticle-Based Drug Delivery Systems.International journal of nanomedicine · 2024Review
- Emerging roles of proximal tubular endocytosis in renal fibrosis.Frontiers in cell and developmental biology · 2023Review
- Identification of Potential Megalin/Cubilin Substrates Using Extensive Proteomics Quantification from Kidney Megalin-Knockdown Mice.The AAPS journal · 2022Article
- Albumin Expands Albumin Reabsorption Capacity in Proximal Tubule Epithelial Cells through a Positive Feedback Loop between AKT and Megalin.International journal of molecular sciences · 2022Article
- The effect of eight weeks of moderate and high intensity aerobic training on the gene expression of Mir-145, Wnt3a and Dab2 in the heart tissue of type 2 diabetic rats.Journal of diabetes and metabolic disorders · 2021Article
- Renal Handling of Albumin-From Early Findings to Current Concepts.International journal of molecular sciences · 2021Review
- Integrin αIIbβ3 outside-in signaling activates human platelets through serine 24 phosphorylation of Disabled-2.Cell & bioscience · 2021Article
- Article
- Receptor-Mediated Endocytosis in the Proximal Tubule.Annual review of physiology · 2017Review
- Predicting physiologically relevant SH3 domain mediated protein-protein interactions in yeast.Bioinformatics (Oxford, England) · 2016Article
- The adaptor protein Disabled-2: new insights into platelet biology and integrin signaling.Thrombosis journal · 2016Review
- Akt Links Insulin Signaling to Albumin Endocytosis in Proximal Tubule Epithelial Cells.PloS one · 2015Article
- Dynamic multimerization of Dab2-Myosin VI complexes regulates cargo processivity while minimizing cortical actin reorganization.The Journal of biological chemistryArticle
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
Proximal tubule epithelial cells have a highly sophisticated endocytic machinery to retrieve the albumin in the glomerular filtrate. The megalin-cubilin complex and the endocytic adaptor disabled-2 (Dab2) play a pivotal role in albumin endocytosis. We previously demonstrated that protein kinase B (Akt) regulates albumin endocytosis in the proximal tubule through an interaction with Dab2. Here, we examined the nature of Akt-Dab2 interaction. The pleckstrin homology (PH) and catalytic domains (CD) of Akt interacted with the proline-rich domain (PRD) of Dab2 based on yeast-two hybrid (Y2H) experiments. Pull-down experiments utilizing the truncated constructs of Dab2 demonstrated that the initial 11 amino acids of Dab2-PRD were sufficient to mediate the interaction between Akt and Dab2. Endocytosis experiments utilizing Akt1- and Akt2-silencing RNA revealed that both Akt1 and Akt2 mediate albumin endocytosis in proximal tubule epithelial cells; therefore, Akt1 and Akt2 may play a compensatory role in albumin endocytosis. Furthermore, both Akt isoforms phosphorylated Dab2 at Ser residues 448 and 449. Ser-to-Ala mutations of these Dab2 residues inhibited albumin endocytosis and resulted in a shift in location of Dab2 from the peripheral to the perinuclear area, suggesting the physiological relevance of these phosphorylation sites in albumin endocytosis. We conclude that both Akt1 and Akt2 are involved in albumin endocytosis, and phosphorylation of Dab2 by Akt induces albumin endocytosis in proximal tubule epithelial cells. Further delineation of how Akt affects expression/phosphorylation of endocytic adaptors and receptors will enhance our understanding of the molecular network triggered by albumin overload in the proximal tubule.
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Registered trials
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.