ArticleMolecular biology of the cell2007
A novel AAK1 splice variant functions at multiple steps of the endocytic pathway.
Article in Molecular biology of the cell, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
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- WNT Activates the AAK1 Kinase to Promote Clathrin-Mediated Endocytosis of LRP6 and Establish a Negative Feedback Loop.Cell reports · 2019Article
- Viral journeys on the intracellular highways.Cellular and molecular life sciences : CMLS · 2018Review
- Ndr kinases regulate retinal interneuron proliferation and homeostasis.Scientific reports · 2018Article
- Decoding Common Features of Neurodegenerative Disorders: From Differentially Expressed Genes to Pathways.Current genomics · 2018Article
- Non-canonical Functions of Macroautophagy Proteins During Endocytosis by Myeloid Antigen Presenting Cells.Frontiers in immunology · 2018Review
- The autophagy machinery restrains iNKT cell activation through CD1D1 internalization.Autophagy · 2017Article
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- Family-wide Structural Analysis of Human Numb-Associated Protein Kinases.Structure (London, England : 1993) · 2016Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phosphorylation is a critical step in regulating receptor transport through the endocytic pathway. AAK1 is a serine/threonine kinase that is thought to coordinate the recruitment of AP-2 to receptors containing tyrosine-based internalization motifs by phosphorylating the micro2 subunit. Here we have identified a long form of AAK1 (AAK1L) that contains an extended C-terminus that encodes an additional clathrin-binding domain (CBD2) consisting of multiple low-affinity interaction motifs. Protein interaction studies demonstrate that AAK1L CBD2 directly binds clathrin. However, in vitro kinase assays reveal little difference between AAK1 isoforms in their basal or clathrin-stimulated kinase activity toward the AP-2 micro2 subunit. However, overexpression of AAK1L CBD2 impairs transferrin endocytosis, confirming an endocytic role for AAK1. Surprisingly, CBD2 overexpression or AAK1 depletion by RNA interference significantly impairs transferrin recycling from the early/sorting endosome. These observations suggest that AAK1 functions at multiple steps of the endosomal pathway by regulating transferrin internalization and its rapid recycling back to the plasma membrane from early/sorting endosome.
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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.