Identification of centaurin-2: a phosphatidylinositide-binding protein present in fat, heart and skeletal muscle

Authors: Whitley P.¹; Gibbard A.M.¹; Koumanov F.¹; Oldfield S.¹; Kilgour E.E.²; Prestwich G.D.³; Holman G.D.¹

Source: European Journal of Cell Biology, Volume 81, Number 4, April 2002 , pp. 222-230(9)

Publisher: Urban & Fischer

Abstract:

We describe here the cloning, expression and characterisation of centaurin-2 from a rat adipocyte cDNA library. The centaurin-2 cDNA contains an open reading frame, which codes for a protein of 376 amino acids with predicted mass of 43.5 kDa. Centaurin-2 shares 51 – 59% identity with centaurin-1 proteins and has the same domain organisation, consisting of a predicted N-terminal ArfGAP domain followed by two successive pleckstrin homology domains. Despite the sequence similarity, there are a number of notable differences between the previously characterised centaurin-1 proteins and the newly described centaurin-2: (i) in vitro lipid binding experiments with centaurin-2 do not reveal the same selectivity for phosphatidylinositol 3,4,5-trisphosphate over phosphatidylinositol 4,5-bisphosphate that has been shown for centaurin-1; (ii) unlike centaurin-1 which is expressed mainly in the brain, centaurin-2 has a broad tissue distribution, being particularly abundant in fat, heart and skeletal muscle; (iii) in contrast to centaurin-1 which is found in both membrane and cytosolic fractions, endogenous centaurin-2 is exclusively present in the dense membrane fractions of cell extracts, suggesting a constitutive membrane association. Insulin stimulation, which stimulates phosphatidylinositol 3,4,5-trisphosphate production, does not alter the subcellular distribution of centaurin-2 between adipocyte membrane fractions. This observation is consistent with the lack of specificity of centaurin-2 for phosphatidylinositol 3,4,5-trisphosphate over phosphatidylinositol 4,5-bisphosphate.

Keywords: Centaurin; PH domains; IP4; phosphatidylinositides; adipose; heart; muscle

Language: English

Document Type: Original article

DOI: http://dx.doi.org/10.1078/0171-9335-00242

Affiliations: 1: Department of Biology and Biochemistry, University of Bath, Bath/United Kingdom 2: Cardiovascular and Gastrointestinal Research Department, AstraZeneca Pharmaceuticals, Macclesfield, Cheshire/United Kingdom 3: Department of Medicinal Chemistry, University of Utah, Salt Lake City, Utah/USA

Publication date: 2002-04-01

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• By this author: Whitley P. ;  Gibbard A.M. ;  Koumanov F. ;  Oldfield S. ;  Kilgour E.E. ;  Prestwich G.D. ;  Holman G.D.

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