Open AccessPED/PEA‐15 interacts with the 67 kD laminin receptor and regulates cell adhesion, migration, proliferation and apoptosis
Author(s) -
Formisano Pietro,
Ragno Pia,
Pesapane Ada,
Alfano Daniela,
Alberobello Anna Teresa,
Rea Vincenza Elena Anna,
Giusto Raffaella,
Rossi Francesca W.,
Beguinot Francesco,
Rossi Guido,
Montuori Nunzia
Publication year - 2012
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2011.01411.x
Subject(s) - laminin , hek 293 cells , transfection , biology , cell adhesion , phosphoprotein , extracellular matrix , microbiology and biotechnology , integrin , cell growth , apoptosis , cell , receptor , cell migration , cell culture , phosphorylation , biochemistry , genetics
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.