Identification of DOCK4 and its splicing variant as PIP3 binding proteins.
DOCK4, 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.
Kanai
Akinori
A
Division of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
Ihara
Sayoko
S
Ohdaira
Tsutomu
T
Shinohara-Kanda
Azusa
A
Iwamatsu
Akihiro
A
Fukui
Yasuhisa
Y
D017398:Alternative Splicing; D002352:Carrier Proteins; D002460:Cell Line; D003001:Cloning, Molecular; D005091:Exons; D020690:GTPase-Activating Proteins / Q000737:chemistry*; D005786:Gene Expression Regulation; D006801:Humans; D018613:Microscopy, Confocal; D008954:Models, Biological; D009154:Mutation; D011485:Protein Binding; D020033:Protein Isoforms; D014162:Transfection; D020744:rac GTP-Binding Proteins / Q000737:chemistry*
D002352:Carrier Proteins; C099818:DOCK1 protein, human; C510122:DOCK4 protein, human; D020690:GTPase-Activating Proteins; D020033:Protein Isoforms; D020744:rac GTP-Binding Proteins