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.