title: PED/PEA-15 interacts with the 67 kD laminin receptor and regulates cell adhesion, migration, proliferation and apoptosis.
abstract: Phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes-15 kD (PED/PEA-15) is an anti-apoptotic protein whose expression is increased in several human cancers. In addition to apoptosis, PED/PEA-15 is involved in the regulation of other major cellular functions, including cell adhesion, migration, proliferation and glucose metabolism. To further understand the functions of this protein, we performed a yeast two-hybrid screening using PED/PEA-15 as a bait and identified the 67 kD high-affinity laminin receptor (67LR) as an interacting partner. 67 kD laminin receptor is a non-integrin cell-surface receptor for the extracellular matrix (ECM), derived from the dimerization of a 37 kD cytosolic precursor (37LRP). The 67LR is highly expressed in human cancers and widely recognized as a molecular marker of metastatic aggressiveness. The molecular interaction of PED/PEA-15 with 67LR was confirmed by pull-down experiments with recombinant His-tagged 37LRP on lysates of PED/PEA-15 transfected HEK-293 cells. Further, overexpressed or endogenous PED/PEA-15 was co-immunoprecipitated with 67LR in PED/PEA-15-transfected HEK-293 cells and in U-373 glioblastoma cells, respectively. PED/PEA-15 overexpression significantly increased 67LR-mediated HEK-293 cell adhesion and migration to laminin that, in turn, determined PED/PEA-15 phosphorylation both in Ser-104 and Ser-116, thus enabling cell proliferation and resistance to apoptosis. PED/PEA-15 ability to induce cell responses to ECM-derived signals through interaction with 67LR may be of crucial importance for tumour cell survival in a poor microenvironment, thus favouring the metastatic spread and colonization.
authors: Department of Cellular and Molecular Biology and Pathology, Federico II University, Naples, taly.
authors: Pietro
authors: P
authors: Formisano
authors: Pia
authors: P
authors: Ragno
authors: Ada
authors: A
authors: Pesapane
authors: Daniela
authors: D
authors: Alfano
authors: Anna Teresa
authors: AT
authors: Alberobello
authors: Vincenza Elena Anna
authors: VE
authors: Rea
authors: Raffaella
authors: R
authors: Giusto
authors: Francesca W
authors: FW
authors: Rossi
authors: Francesco
authors: F
authors: Beguinot
authors: Guido
authors: G
authors: Rossi
authors: Nunzia
authors: N
authors: Montuori
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001253:Astrocytes; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival; D005109:Extracellular Matrix / Q000378:metabolism; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D005909:Glioblastoma / Q000473:pathology; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D007797:Laminin / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017474:Receptors, Laminin / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D051017:Apoptosis Regulatory Proteins; D047908:Intracellular Signaling Peptides and Proteins; D007797:Laminin; C092039:PEA15 protein, human; D010750:Phosphoproteins; D017474:Receptors, Laminin