Lp. Hammondsodie et al., IDENTIFICATION AND CLONING OF CENTAURIN-ALPHA - A NOVEL PHOSPHATIDYLINOSITOL 3,4,5-TRISPHOSPHATE-BINDING PROTEIN FROM RAT-BRAIN, The Journal of biological chemistry, 271(31), 1996, pp. 18859-18868
Using an affinity resin and photoaffinity label based on phospholipid
analogs of inositol 1,3,4,5-tetrakisphosphate (InsP(4)), we have isola
ted, characterized, and cloned a 46-kDa protein from rat brain, which
we have named centaurin-alpha. Binding specificity was determined usin
g displacement of H-3](3-[4-benzoyldihydrocinnamidyl]propyl)-InsP(4) p
hotoaffinity labeling. Centaurin-alpha displayed highest affinity for
phosphatidylinositol 3,4,5-trisphosphate (PtdInsP(3)) (IC50 = 120 nm),
whereas InsP(4), PtdInsP(2), and InsP(3) bound with 5-, 12-, and >50-
fold lower affinity, respectively. Screening a rat brain cDNA library
with a polymerase chain reaction product, generated using partial amin
o acid sequence from tryptic peptides, yielded a full-length clone. Th
e 2,450-base pair cDNA contained an open reading frame (ORF) encoding
a novel protein of 419 amino acids. Northern analysis revealed a 2.5-k
ilobase transcript that is highly expressed in brain. The deduced sequ
ence contains a novel putative zinc finger motif, 10 ankyrin-like repe
ats, and shows homology to recently identified yeast and mammalian Arf
GTPase-activating proteins. Given the specificity of binding and enri
chment in brain, centaurin-alpha is a candidate PtdInsP(3) receptor th
at may link the activation of phosphoinositide 3-kinase to downstream
responses in the brain.