The tyrosine kinase ACK1 associates with clathrin-coated vesicles through a binding motif shared by arrestin and other adaptors

One target for the small GTPase Cdc42 is the nonreceptor tyrosine kinase ac tivated Cdc42-associated kinase (ACK), which binds selectively to Cdc42.GTP . We report that ACK1 can associate directly with the heavy chain of clathr in. A central region in ACK1 containing a conserved motif behaves as a clat hrin adaptor and competes with beta -arrestin for a common binding site on the clathrin N-terminal head domain. Overexpressed ACK1 perturbs clathrin d istribution, an activity dependent on the presence of C-terminal "adaptor" sequences that are also present in the related nonkinase gene 33, ACK1 inte racts with the adaptor Nck via SH3 interactions but does not form a trimeri c complex with p21-activated serine/threonine kinase, which also binds Nck, Stable low level expression of green fluorescent protein-ACK1 in NIH 3T3 c ells has been used to localize ACK1 to clathrin-containing vesicles. The cc -localization of ACK1 in vivo with clathrin and AP-2 indicates that it part icipates in trafficking, underlying an ability to increase receptor-mediate d transferrin uptake.