title: Structure-function relationships of phosphatidylinositol transfer proteins: involvement of phosphorylation sites.
abstract: The mammalian low molecular weight phosphatidylinositol transfer proteins: PI-TPalpha and PI-TPbeta are extremely well conserved and highly homologous. Surprisingly, the two proteins clearly show different cellular localizations and display contrary physiological functions. Phosphorylation of the proteins might be the regulatory factor to ensure the selective cellular functions. A major difference between PI-TPalpha and PI-TPbeta is the capacity of PI-TPbeta to bind and transfer sphingomyelin (SM) in vivo. This activity is correlated with phosphorylation of Ser262, which is only present in PI-TPbeta. Structural aspects of phosphorylation sites of PI-TPs are analyzed in order to find an explanation for the functional data. We propose that phosphorylation of one serine residue (Ser165/166) in both PI-TPalpha and PI-TPbeta is involved in the regulation of membrane binding of all PI-TPs and that phosphorylation of the unique Ser262 in PI-TPbeta-like proteins ensures the right cellular localization of PI-TPbetas that is necessary for the specific activity at the Golgi membrane.
authors.affiliation: Department Biochemistry of Lipids, CBLE, University of Utrecht, Padualaan 8, De Uithof, Utrecht, The Netherlands. g.t.snoek@chem.uu.nl <g.t.snoek@chem.uu.nl>
authors.forename: Gerry T
authors.initials: GT
authors.lastname: Snoek
authors.forename: Claudia M
authors.initials: CM
authors.lastname: Van Tiel
authors.forename: Maarten R
authors.initials: MR
authors.lastname: Egmond
mesh_terms: D000818:Animals; D006801:Humans; D049294:Phospholipid Transfer Proteins / Q000737:chemistry* / Q000502:physiology*; D010766:Phosphorylation; D011485:Protein Binding / Q000502:physiology; D011487:Protein Conformation; D020033:Protein Isoforms / Q000737:chemistry / Q000502:physiology; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
chemical_list: D049294:Phospholipid Transfer Proteins; D020033:Protein Isoforms