The Tyrosine Kinase ACK1 Associates with Clathrin-coated Vesicles through a Binding Motif Shared by Arrestin and Other Adaptors

• Published in: The Journal of biological chemistry 2001-05, Vol.276 (21), p.18392-18398
• Main Authors: Teo, Mabel, Tan, Lydia, Lim, Louis, Manser, Edward
• Format: Article
• Language: English
• Subjects: 3T3 Cells; Adaptor Protein Complex alpha Subunits; Adaptor Proteins, Vesicular Transport; Animals; Arrestin - metabolism; Biological Transport; Clathrin - metabolism; Clathrin-Coated Vesicles - metabolism; COS Cells; Endocytosis; Membrane Proteins - metabolism; Mice; Protein-Tyrosine Kinases - metabolism; Signal Transduction
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M008795200

One target for the small GTPase Cdc42 is the nonreceptor tyrosine kinase activated Cdc42-associated kinase (ACK), which binds selectively to Cdc42·GTP. We report that ACK1 can associate directly with the heavy chain of clathrin. A central region in ACK1 containing a conserved motif behaves as a clathrin adaptor and competes with β-arrestin for a common binding site on the clathrin N-terminal head domain. Overexpressed ACK1 perturbs clathrin distribution, an activity dependent on the presence of C-terminal “adaptor” sequences that are also present in the related nonkinase gene 33. ACK1 interacts with the adaptor Nck via SH3 interactions but does not form a trimeric complex with p21-activated serine/threonine kinase, which also binds Nck. Stable low level expression of green fluorescent protein-ACK1 in NIH 3T3 cells has been used to localize ACK1 to clathrin-containing vesicles. The co-localization of ACK1in vivo with clathrin and AP-2 indicates that it participates in trafficking, underlying an ability to increase receptor-mediated transferrin uptake.