PMID- 10448098 OWN - NLM STAT- MEDLINE DCOM- 19990923 LR - 20191210 IS - 0006-291X (Print) IS - 0006-291X (Linking) VI - 262 IP - 1 DP - 1999 Aug 19 TI - Molecular cloning and functional characterization of a human homologue of centaurin-alpha. PG - 237-44 AB - We report here the molecular cloning, expression, and characterisation of a human homologue of rat centaurin-alpha, which we have termed centaurin-alpha(1). The cDNA contains a single open reading frame, which encodes a 373-amino-acid protein with a calculated molecular weight of 43,429 Daltons. Centaurin-alpha(1) shows high identity at the amino acid level with the other centaurin-alpha homologues, p42(IP4) and PIP(3)BP. Northern analysis revealed that centaurin-alpha(1) expresses as a single 2.5-kb transcript, mainly in the brain. Recombinant centaurin-alpha(1) binds the inositol head group of PtdIns(3,4,5)P(3) and Ins(1,3,4, 5)P(4), with high affinity (K(d) 139.7 +/- 10.5 nM) and inositol phosphate specificity, consistent with it functioning as a putative PtdIns(3,4,5)P(3) receptor. In keeping with this conclusion, we have shown that GFP-tagged centaurin-alpha(1) recruits to the plasma membrane in a PI 3-kinase-dependent manner and the recruitment is inhibited by the PI 3-kinase inhibitor wortmannin. These results suggest that centaurin-alpha(1) can function as an in vivo PtdIns(3, 4,5)P(3) receptor. CI - Copyright 1999 Academic Press. FAU - Venkateswarlu, K AU - Venkateswarlu K AD - School of Medical Sciences, University of Bristol, Bristol, BS8 1TD, United Kingdom. FAU - Cullen, P J AU - Cullen PJ LA - eng SI - GENBANK/AJ006422 PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (ADAP1 protein, human) RN - 0 (Adap1 protein, rat) RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Androstadienes) RN - 0 (Carrier Proteins) RN - 0 (GTPase-Activating Proteins) RN - 0 (Inositol Phosphates) RN - 0 (Nerve Tissue Proteins) RN - 0 (Phosphatidylinositol Phosphates) RN - 0 (Phosphoinositide-3 Kinase Inhibitors) RN - 0 (RNA, Messenger) RN - 0 (Recombinant Fusion Proteins) RN - 0 (phosphatidylinositol 3,4,5-triphosphate) RN - 102850-29-3 (inositol-1,3,4,5-tetrakisphosphate) RN - XVA4O219QW (Wortmannin) SB - IM MH - Adaptor Proteins, Signal Transducing MH - Amino Acid Sequence MH - Androstadienes/pharmacology MH - Animals MH - Base Sequence MH - Binding Sites MH - Brain/metabolism MH - CHO Cells MH - Carrier Proteins/chemistry/*genetics/metabolism MH - Cell Membrane/drug effects/metabolism MH - Cloning, Molecular MH - Cricetinae MH - GTPase-Activating Proteins MH - Humans MH - Inositol Phosphates/metabolism MH - Molecular Sequence Data MH - Nerve Tissue Proteins/chemistry/*genetics/metabolism MH - Organ Specificity MH - Phosphatidylinositol 3-Kinases/metabolism MH - Phosphatidylinositol Phosphates/metabolism MH - Phosphoinositide-3 Kinase Inhibitors MH - RNA, Messenger/analysis/genetics MH - Recombinant Fusion Proteins/metabolism MH - Sequence Homology, Amino Acid MH - Wortmannin MH - Zinc Fingers EDAT- 1999/08/17 00:00 MHDA- 1999/08/17 00:01 CRDT- 1999/08/17 00:00 PHST- 1999/08/17 00:00 [pubmed] PHST- 1999/08/17 00:01 [medline] PHST- 1999/08/17 00:00 [entrez] AID - 10.1006/bbrc.1999.1065 [doi] AID - S0006-291X(99)91065-3 [pii] PST - ppublish SO - Biochem Biophys Res Commun. 1999 Aug 19;262(1):237-44. doi: 10.1006/bbrc.1999.1065.