Interaction of the PDZ domain of human PICK1 with class I ADP-ribosylationfactors

We have cloned the cDNA encoding human PICK1 (protein interacting with C ki nase 1), a PDZ domain-containing protein of 415 amino acids, and also ident ified the Drosophila homologue by search of the databank, Northern blot ana lysis shows a single mRNA of about 2.0 kb ubiquitously expressed in human t issues, Although PICK1 proteins harbor a region homologous to arfaptin1 and arfaptin2, two proteins that bind to the ARF (ADP-ribosylation factor), th is region of PICK1 does not interact with ARFs in the yeast two-hybrid syst em. On the other hand, the PDZ domain of PICK1 is capable of interacting wi th constitutively active, GTP-bound forms of ARF1 and ARF3, but neither wit h those of ARF5/6 nor with the GDP-bound ARFs, The PICK1-ARF interaction is abrogated by introduction of mutations in the PDZ domain or by deletion of the extreme C-terminus of ARF1, Thus, PICK1 specifically interacts with AR F1/3 in the GTP-bound state, suggesting that PICK1 participates in ARF1/3-m ediated cellular processes, (C) 2000 Academic Press.