Identification of an adaptor-associated kinase, AAK1, as a regulator of clathrin-mediated endocytosis

doi:10.1083/jcb.200108123

Published 4 March 2002. doi:10.1083/jcb.200108123

This Article

Full Text

Full Text (PDF, 507K)

PPT slides of all figures

Alert me when this article is cited

Citation Map

Services

Email this article

Similar articles in this journal

Similar articles in PubMed

Alert me to new content in the JCB

Download to citation manager

Citing Articles

Citing Articles via HighWire

Citing Articles via CrossRef

Citing Articles via Google Scholar

Google Scholar

Articles by Conner, S. D.

Articles by Schmid, S. L.

Search for Related Content

PubMed

PubMed Citation

Articles by Conner, S. D.

Articles by Schmid, S. L.

Pubmed/NCBI databases

Gene	GEO Profiles
HomoloGene	Protein
UniGene
Substance via MeSH

Related Collections

Related Article

Social Bookmarking

What's this?

© The Rockefeller University Press, 0021-9525/2002/3/921 $5.00
The Journal of Cell Biology, Volume 156, Number 5, March 4, 2002 921-929

Article

Identification of an adaptor-associated kinase, AAK1, as a regulator of clathrin-mediated endocytosis

Sean D. Conner and Sandra L. Schmid

The Scripps Research Institute, La Jolla, CA 92037

Address correspondence to Sandra L. Schmid, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037. Tel.: (858) 784-2311. Fax: (858) 784-9126. E-mail: slschmid{at}scripps.edu

The µ2 subunit of the AP2 complex is known to be phosphorylatedin vitro by a copurifying kinase, and it has been demonstratedrecently that µ2 phosphorylation is required for transferrinendocytosis (Olusanya, O., P.D. Andrews, J.R. Swedlow, and E.Smythe. 2001. Curr. Biol. 11:896–900). However, the identityof the endogenous kinase responsible for this phosphorylationis unknown. Here we identify and characterize a novel memberof the Prk/Ark family of serine/threonine kinases, adaptor-associatedkinase (AAK)1. We find that AAK1 copurifies with adaptor protein(AP)2 and that it directly binds the ear domain of ${alpha}$ -adaptinin vivo and in vitro. In neuronal cells, AAK1 is enriched atpresynaptic terminals, whereas in nonneuronal cells it colocalizeswith clathrin and AP2 in clathrin-coated pits and at the leadingedge of migrating cells. AAK1 specifically phosphorylates theµ subunit in vitro, and stage-specific assays for endocytosisshow that µ phosphorylation by AAK1 results in a decreasein AP2-stimulated transferrin internalization. Together, theseresults provide strong evidence that AAK1 is the endogenousµ2 kinase and plays a regulatory role in clathrin-mediatedendocytosis. These results also lend support to the idea thatclathrin-mediated endocytosis is controlled by cycles of phosphorylation/desphosphorylation.

Key Words: AAK1; AP2; clathrin; kinase; endocytosis

Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?

Related Article

A kinase kick for endocytosis: Nicole LeBrasseur
J. Cell Biol. 2002 156: 767. [Full Text] [PDF]

This article has been cited by other articles:

Rollason, R., Korolchuk, V., Hamilton, C., Jepson, M., Banting, G. (2009). A CD317/tetherin-RICH2 complex plays a critical role in the organization of the subapical actin cytoskeleton in polarized epithelial cells. JCB 184: 721-736 [Abstract] [Full Text]
Semerdjieva, S., Shortt, B., Maxwell, E., Singh, S., Fonarev, P., Hansen, J., Schiavo, G., Grant, B. D., Smythe, E. (2008). Coordinated regulation of AP2 uncoating from clathrin-coated vesicles by rab5 and hRME-6. JCB 183: 499-511 [Abstract] [Full Text]
Hitchcock, I. S., Chen, M. M., King, J. R., Kaushansky, K. (2008). YRRL motifs in the cytoplasmic domain of the thrombopoietin receptor regulate receptor internalization and degradation. Blood 112: 2222-2231 [Abstract] [Full Text]
Ricotta, D., Hansen, J., Preiss, C., Teichert, D., Honing, S. (2008). Characterization of a Protein Phosphatase 2A Holoenzyme That Dephosphorylates the Clathrin Adaptors AP-1 and AP-2. J. Biol. Chem. 283: 5510-5517 [Abstract] [Full Text]
Zeng, G., Huang, B., Neo, S. P., Wang, J., Cai, M. (2007). Scd5p Mediates Phosphoregulation of Actin and Endocytosis by the Type 1 Phosphatase Glc7p in Yeast. Mol. Biol. Cell 18: 4885-4898 [Abstract] [Full Text]
Kametaka, S., Moriyama, K., Burgos, P. V., Eisenberg, E., Greene, L. E., Mattera, R., Bonifacino, J. S. (2007). Canonical Interaction of Cyclin G associated Kinase with Adaptor Protein 1 Regulates Lysosomal Enzyme Sorting. Mol. Biol. Cell 18: 2991-3001 [Abstract] [Full Text]
Henderson, D. M., Conner, S. D. (2007). A Novel AAK1 Splice Variant Functions at Multiple Steps of the Endocytic Pathway. Mol. Biol. Cell 18: 2698-2706 [Abstract] [Full Text]
Zhu, J., Yu, D., Zeng, X.-C., Zhou, K., Zhan, X. (2007). Receptor-mediated Endocytosis Involves Tyrosine Phosphorylation of Cortactin. J. Biol. Chem. 282: 16086-16094 [Abstract] [Full Text]
Allaire, P. D., Ritter, B., Thomas, S., Burman, J. L., Denisov, A. Yu., Legendre-Guillemin, V., Harper, S. Q., Davidson, B. L., Gehring, K., McPherson, P. S. (2006). Connecdenn, A Novel DENN Domain-Containing Protein of Neuronal Clathrin-Coated Vesicles Functioning in Synaptic Vesicle Endocytosis. J. Neurosci. 26: 13202-13212 [Abstract] [Full Text]
Takahashi, T., Furuchi, T., Naganuma, A. (2006). Endocytic Ark/Prk Kinases Play a Critical Role in Adriamycin Resistance in Both Yeast and Mammalian Cells. Cancer Res. 66: 11932-11937 [Abstract] [Full Text]
Motley, A. M., Berg, N., Taylor, M. J., Sahlender, D. A., Hirst, J., Owen, D. J., Robinson, M. S. (2006). Functional Analysis of AP-2 {alpha} and {micro}2 Subunits. Mol. Biol. Cell 17: 5298-5308 [Abstract] [Full Text]
Smythe, E., Ayscough, K. R. (2006). Actin regulation in endocytosis. J. Cell Sci. 119: 4589-4598 [Abstract] [Full Text]
Kim, S. H., Choi, H. J., Lee, K. W., Hong, N. H., Sung, B. H., Choi, K. Y., Kim, S.-M., Chang, S., Eom, S. H., Song, W. K. (2006). Interaction of SPIN90 with syndapin is implicated in clathrin-mediated endocytic pathway in fibroblasts.. GENES CELLS 11: 1197-1211 [Abstract] [Full Text]
Duwel, M., Ungewickell, E. J. (2006). Clathrin-dependent Association of CVAK104 with Endosomes and the Trans-Golgi Network. Mol. Biol. Cell 17: 4513-4525 [Abstract] [Full Text]
Bairstow, S. F., Ling, K., Su, X., Firestone, A. J., Carbonara, C., Anderson, R. A. (2006). Type I{gamma}661 Phosphatidylinositol Phosphate Kinase Directly Interacts with AP2 and Regulates Endocytosis. J. Biol. Chem. 281: 20632-20642 [Abstract] [Full Text]
Collawn, J. F. (2006). Unlocking the Mysteries of Na+-K+-ATPase Endocytosis: Phosphorylation Is the Key.. Am. J. Respir. Cell Mol. Bio. 35: 1-2 [Full Text]
Chen, Z., Krmar, R. T., Dada, L., Efendiev, R., Leibiger, I. B., Pedemonte, C. H., Katz, A. I., Sznajder, J. I., Bertorello, A. M. (2006). Phosphorylation of Adaptor Protein-2 {micro}2 Is Essential for Na+,K+-ATPase Endocytosis in Response to Either G Protein-Coupled Receptor or Reactive Oxygen Species. Am. J. Respir. Cell Mol. Bio. 35: 127-132 [Abstract] [Full Text]
Schmidt, U., Briese, S., Leicht, K., Schurmann, A., Joost, H.-G., Al-Hasani, H. (2006). Endocytosis of the glucose transporter GLUT8 is mediated by interaction of a dileucine motif with the {beta}2-adaptin subunit of the AP-2 adaptor complex. J. Cell Sci. 119: 2321-2331 [Abstract] [Full Text]
Huang, T., Wolkoff, A. W., Stockert, R. J. (2006). Adaptor heat shock protein complex formation regulates trafficking of the asialoglycoprotein receptor. Am. J. Physiol. Gastrointest. Liver Physiol. 290: G369-G376 [Abstract] [Full Text]
Mitsunari, T., Nakatsu, F., Shioda, N., Love, P. E., Grinberg, A., Bonifacino, J. S., Ohno, H. (2005). Clathrin Adaptor AP-2 Is Essential for Early Embryonal Development. Mol. Cell. Biol. 25: 9318-9323 [Abstract] [Full Text]
Kametaka, S., Mattera, R., Bonifacino, J. S. (2005). Epidermal Growth Factor-Dependent Phosphorylation of the GGA3 Adaptor Protein Regulates Its Recruitment to Membranes. Mol. Cell. Biol. 25: 7988-8000 [Abstract] [Full Text]
Lee, D.-w., Zhao, X., Zhang, F., Eisenberg, E., Greene, L. E. (2005). Depletion of GAK/auxilin 2 inhibits receptor-mediated endocytosis and recruitment of both clathrin and clathrin adaptors. J. Cell Sci. 118: 4311-4321 [Abstract] [Full Text]
Conner, S. D., Schmid, S. L. (2005). CVAK104 Is a Novel Poly-L-lysine-stimulated Kinase That Targets the {beta}2-Subunit of AP2. J. Biol. Chem. 280: 21539-21544 [Abstract] [Full Text]
Yim, Y.-I., Scarselletta, S., Zang, F., Wu, X., Lee, D.-w., Kang, Y.-s., Eisenberg, E., Greene, L. E. (2005). Exchange of clathrin, AP2 and epsin on clathrin-coated pits in permeabilized tissue culture cells. J. Cell Sci. 118: 2405-2413 [Abstract] [Full Text]
Mishra, S. K., Keyel, P. A., Edeling, M. A., Dupin, A. L., Owen, D. J., Traub, L. M. (2005). Functional Dissection of an AP-2 {beta}2 Appendage-binding Sequence within the Autosomal Recessive Hypercholesterolemia Protein. J. Biol. Chem. 280: 19270-19280 [Abstract] [Full Text]
Mishra, S. K., Hawryluk, M. J., Brett, T. J., Keyel, P. A., Dupin, A. L., Jha, A., Heuser, J. E., Fremont, D. H., Traub, L. M. (2004). Dual Engagement Regulation of Protein Interactions with the AP-2 Adaptor {alpha} Appendage. J. Biol. Chem. 279: 46191-46203 [Abstract] [Full Text]
Zhang, L., Gjoerup, O., Roberts, T. M. (2004). The serine/threonine kinase cyclin G-associated kinase regulates epidermal growth factor receptor signaling. Proc. Natl. Acad. Sci. USA 101: 10296-10301 [Abstract] [Full Text]
Blondeau, F., Ritter, B., Allaire, P. D., Wasiak, S., Girard, M., Hussain, N. K., Angers, A., Legendre-Guillemin, V., Roy, L., Boismenu, D., Kearney, R. E., Bell, A. W., Bergeron, J. J. M., McPherson, P. S. (2004). Tandem MS analysis of brain clathrin-coated vesicles reveals their critical involvement in synaptic vesicle recycling. Proc. Natl. Acad. Sci. USA 101: 3833-3838 [Abstract] [Full Text]
Jha, A., Agostinelli, N. R., Mishra, S. K., Keyel, P. A., Hawryluk, M. J., Traub, L. M. (2004). A Novel AP-2 Adaptor Interaction Motif Initially Identified in the Long-splice Isoform of Synaptojanin 1, SJ170. J. Biol. Chem. 279: 2281-2290 [Abstract] [Full Text]
Chan, S.-A., Smith, C. (2003). Low frequency stimulation of mouse adrenal slices reveals a clathrin-independent, protein kinase C-mediated endocytic mechanism. J. Physiol. 553: 707-717 [Abstract] [Full Text]
Huang, B., Zeng, G., Ng, A. Y.J., Cai, M. (2003). Identification of Novel Recognition Motifs and Regulatory Targets for the Yeast Actin-regulating Kinase Prk1p. Mol. Biol. Cell 14: 4871-4884 [Abstract] [Full Text]
Traub, L. M. (2003). Sorting it out: AP-2 and alternate clathrin adaptors in endocytic cargo selection. JCB 163: 203-208 [Abstract] [Full Text]
Jackson, A. P., Flett, A., Smythe, C., Hufton, L., Wettey, F. R., Smythe, E. (2003). Clathrin promotes incorporation of cargo into coated pits by activation of the AP2 adaptor {micro}2 kinase. JCB 163: 231-236 [Abstract] [Full Text]
Sekiya-Kawasaki, M., Groen, A. C., Cope, M. J. T.V., Kaksonen, M., Watson, H. A., Zhang, C., Shokat, K. M., Wendland, B., McDonald, K. L., McCaffery, J. M., Drubin, D. G. (2003). Dynamic phosphoregulation of the cortical actin cytoskeleton and endocytic machinery revealed by real-time chemical genetic analysis. JCB 162: 765-772 [Abstract] [Full Text]
Conner, S. D., Schmid, S. L. (2003). Differential requirements for AP-2 in clathrin-mediated endocytosis. JCB 162: 773-780 [Abstract] [Full Text]
Ghosh, P., Kornfeld, S. (2003). AP-1 binding to sorting signals and release from clathrin-coated vesicles is regulated by phosphorylation. JCB 160: 699-708 [Abstract] [Full Text]
Wasiak, S., Legendre-Guillemin, V., Puertollano, R., Blondeau, F., Girard, M., de Heuvel, E., Boismenu, D., Bell, A. W., Bonifacino, J. S., McPherson, P. S. (2002). Enthoprotin: a novel clathrin-associated protein identified through subcellular proteomics. JCB 158: 855-862 [Abstract] [Full Text]
Ricotta, D., Conner, S. D., Schmid, S. L., von Figura, K., Honing, S. (2002). Phosphorylation of the AP2 {micro} subunit by AAK1 mediates high affinity binding to membrane protein sorting signals. JCB 156: 791-795 [Abstract] [Full Text]
Ricotta, D., Conner, S. D., Schmid, S. L., von Figura, K., Honing, S. (2002). Phosphorylation of the AP2 {micro} subunit by AAK1 mediates high affinity binding to membrane protein sorting signals. JCB 156: 791-795 [Abstract] [Full Text]