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Originally published as MBC in Press, 10.1091/mbc.E06-09-0831 on May 9, 2007

Vol. 18, Issue 7, 2698-2706, July 2007

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A Novel AAK1 Splice Variant Functions at Multiple Steps of the Endocytic PathwayFormula

Davin M. Henderson, and Sean D. Conner

Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455

Submitted September 18, 2006; Revised April 4, 2007; Accepted April 26, 2007
Monitoring Editor: David Drubin

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 µ2 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 µ2 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.

This was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E06-09-0831) on May 9, 2007.

Formula The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

Address correspondence to: Sean D. Conner (sdconner{at}umn.edu)




This article has been cited by other articles:


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D. Ricotta, J. Hansen, C. Preiss, D. Teichert, and S. Honing
Characterization of a Protein Phosphatase 2A Holoenzyme That Dephosphorylates the Clathrin Adaptors AP-1 and AP-2
J. Biol. Chem., February 29, 2008; 283(9): 5510 - 5517.
[Abstract] [Full Text] [PDF]


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