No abstract

SummaryDOCK4, a member of DOCK180 family proteins, was originally identified as a product of a gene deleted during tumor progression. Although its tumor suppression properties have been reported, the regulation mechanism of this protein has not been fully elucidated. DOCK4 shares two conserved domains called as DHR-1 and DHR-2 domain as other members including DOCK180. Although DHR-1 in DOCK180 is reported to bind to PIP 3 , whether that of DOCK4 exhibits similar function has yet not been examined. In a search for novel PIP 3 binding proteins by the PIP 3 analog beads binding assay, we found that DOCK4 and its novel splicing variant, whose exon1 and exon52 are different from the known one, bind to PIP 3 . Binding assay using deletion mutants of DOCK4 revealed that the binding region falls into the DHR-1 domain. These results raise the possibility that DOCK4 may be regulated by PIP 3 to exert its function.2008 IUBMB IUBMB Life, 60(7): [467][468][469][470][471][472] 2008

Phosphatidylinositol 3,4,5-trisphosphate (PIP(3)) is an important lipid second messenger that mediates various cell responses. We have searched for the nuclear PIP(3) binding proteins using PIP(3) analogue beads. A 33 kD protein was detected in this method, which was identified as ribosomal protein S3a by the mass spectrometric analysis. The recombinant S3a protein bound specifically to PIP(3). S3a localized not only in the cytosol but also in the nucleus. Interestingly, not cytosolic but nuclear S3a bound to PIP(3), suggesting different roles of S3a in the cytosol and the nucleus.