title: Profilin tyrosine phosphorylation in poly-L-proline-binding regions inhibits binding to phosphoinositide 3-kinase in Phaseolus vulgaris.
abstract: The profilin family consists of a group of ubiquitous highly conserved 12-15 kDa eukaryotic proteins that bind actin, phosphoinositides, poly-l-proline (PLP) and proteins with proline-rich motifs. Some proteins with proline-rich motifs form complexes that have been implicated in the dynamics of the actin cytoskeleton and processes such as vesicular trafficking. A major unanswered question in the field is how profilin achieves the required specificity to bind such an array of proteins. It is now becoming clear that profilin isoforms are subject to differential regulation and that they may play distinct roles within the cell. Considerable evidence suggests that these isoforms have different functional roles in the sorting of diverse proteins with proline-rich motifs. All profilins contain highly conserved aromatic residues involved in PLP binding which are presumably implicated in the interaction with proline-rich motif proteins. We have previously shown that profilin is phosphorylated on tyrosine residues. Here, we show that profilin can bind directly to Phaseolus vulgaris phosphoinositide 3-kinase (PI3K) type III. We demonstrate that a new region around Y72 of profilin, as well as the N- and C-terminal PLP-binding domain, recognizes and binds PLP and PI3K. In vitro binding assays indicate that PI3K type III forms a complex with profilin in a manner that depends on the tyrosine phosphorylation status within the proline-rich-binding domain in profilin. Profilin-PI3K type III interaction suggests that profilin may be involved in membrane trafficking and in linking the endocytic pathway with actin reorganization dynamics.
authors.affiliation: Departmento de Biología Molecular de Plantas, Institute de Biotechnología, UNAM, México, Av. Universidad 2001, Chamilpa, Cuernavaca Mor 62210, Mexico.
authors.forename: Rosaura
authors.initials: R
authors.lastname: Aparicio-Fabre
authors.forename: Gabriel
authors.initials: G
authors.lastname: Guillén
authors.forename: Georgina
authors.initials: G
authors.lastname: Estrada
authors.forename: Juan
authors.initials: J
authors.lastname: Olivares-Grajales
authors.forename: Georgina
authors.initials: G
authors.lastname: Gurrola
authors.forename: Federico
authors.initials: F
authors.lastname: Sánchez
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism*; D027805:Phaseolus / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000737:chemistry / Q000378:metabolism*; D051304:Profilins / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D010455:Peptides; D051304:Profilins; D019000:Phosphotyrosine; C011083:polyproline; D019869:Phosphatidylinositol 3-Kinases