PMID- 10333475
OWN - NLM
STAT- MEDLINE
DCOM- 19990729
LR  - 20181113
IS  - 0264-6021 (Print)
IS  - 0264-6021 (Linking)
VI  - 340 ( Pt 2)
DP  - 1999 Jun 1
TI  - Identification of centaurin-alpha1 as a potential in vivo phosphatidylinositol
      3,4,5-trisphosphate-binding protein that is functionally homologous to the yeast 
      ADP-ribosylation factor (ARF) GTPase-activating protein, Gcs1.
PG  - 359-63
AB  - Centaurin-alpha is a 46 kDa in vitro binding protein for the lipid second
      messenger PtdIns(3,4,5)P3. In this report we have addressed whether
      centaurin-alpha1, a human homologue of centaurin-alpha, binds PtdIns(3,4,5)P3 in 
      vivo and furthermore, identified a potential physiological function for
      centaurin-alpha1. Using confocal microscopy of live PC12 cells, transiently
      transfected with a chimera of green fluorescent protein (GFP) fused to the
      N-terminus of centaurin-alpha1 (GFP-centaurin-alpha1), we demonstrated the rapid 
      plasma membrane recruitment of cytosolic GFP-centaurin-alpha1 following
      stimulation with either nerve growth factor or epidermal growth factor. This
      recruitment was dependent on the centaurin-alpha1 pleckstrin homology domains and
      was blocked by the PtdIns(4,5)P2 3-kinase (PI 3-kinase) inhibitors wortmannin
      (100 nM) and LY294002 (50 microM), and also by co-expression with a dominant
      negative p85. Functionally, we demonstrated that centaurin-alpha1 could
      complement a yeast strain deficient in the ADP-ribosylation factor (ARF)
      GTPase-activating protein Gcs1; a complementation that was blocked by mutagenesis
      of conserved cysteine residues within the ARF GTPase-activating protein analogous
      domain of centaurin-alpha1. Taken together, our data demonstrated that
      centaurin-alpha1 could potentially function as an ARF GTPase-activating protein
      that, on agonist stimulation, was recruited to the plasma membrane possibly
      through an ability to interact with PtdIns(3,4,5)P3.
FAU - Venkateswarlu, K
AU  - Venkateswarlu K
AD  - Department of Biochemistry, School of Medical Sciences, University of Bristol,
      University Walk, Bristol BS8 1TD, U.K.
FAU - Oatey, P B
AU  - Oatey PB
FAU - Tavare, J M
AU  - Tavare JM
FAU - Jackson, T R
AU  - Jackson TR
FAU - Cullen, P J
AU  - Cullen PJ
LA  - eng
SI  - GENBANK/AJ006422
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (ADAP1 protein, human)
RN  - 0 (Adap1 protein, rat)
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Blood Proteins)
RN  - 0 (Carrier Proteins)
RN  - 0 (DNA, Complementary)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Fungal Proteins)
RN  - 0 (GCS1 protein, S cerevisiae)
RN  - 0 (GTPase-Activating Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Phosphatidylinositol Phosphates)
RN  - 0 (Phosphoproteins)
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - 0 (phosphatidylinositol 3,4,5-triphosphate)
RN  - 0 (platelet protein P47)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
RN  - EC 3.6.5.2 (ADP-Ribosylation Factors)
SB  - IM
MH  - ADP-Ribosylation Factors
MH  - Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - Base Sequence
MH  - Blood Proteins/metabolism
MH  - Carrier Proteins/genetics/*metabolism
MH  - Cloning, Molecular
MH  - DNA, Complementary
MH  - DNA-Binding Proteins/*metabolism
MH  - Enzyme Activation
MH  - Fungal Proteins/*metabolism
MH  - GTP-Binding Proteins/*metabolism
MH  - *GTPase-Activating Proteins
MH  - Genetic Complementation Test
MH  - Humans
MH  - Microscopy, Confocal
MH  - Molecular Sequence Data
MH  - Mutagenesis, Site-Directed
MH  - Nerve Tissue Proteins/genetics/*metabolism
MH  - PC12 Cells
MH  - Phosphatidylinositol Phosphates/*metabolism
MH  - *Phosphoproteins
MH  - Protein Binding
MH  - Rats
MH  - Saccharomyces cerevisiae/*metabolism
MH  - *Saccharomyces cerevisiae Proteins
PMC - PMC1220257
EDAT- 1999/05/20 00:00
MHDA- 1999/05/20 00:01
CRDT- 1999/05/20 00:00
PHST- 1999/05/20 00:00 [pubmed]
PHST- 1999/05/20 00:01 [medline]
PHST- 1999/05/20 00:00 [entrez]
PST - ppublish
SO  - Biochem J. 1999 Jun 1;340 ( Pt 2):359-63.