PED/PEA-15 interacts with the 67 kD laminin receptor and regulates cell adhesion, migration, proliferation and apoptosis.
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.
Mesh Terms:
Apoptosis, Apoptosis Regulatory Proteins, Astrocytes, Blotting, Western, Cell Adhesion, Cell Movement, Cell Proliferation, Cell Survival, Extracellular Matrix, Flow Cytometry, Gene Expression Regulation, Glioblastoma, HEK293 Cells, Humans, Immunoprecipitation, Intracellular Signaling Peptides and Proteins, Laminin, Phosphoproteins, Phosphorylation, Receptors, Laminin, Transfection
Apoptosis, Apoptosis Regulatory Proteins, Astrocytes, Blotting, Western, Cell Adhesion, Cell Movement, Cell Proliferation, Cell Survival, Extracellular Matrix, Flow Cytometry, Gene Expression Regulation, Glioblastoma, HEK293 Cells, Humans, Immunoprecipitation, Intracellular Signaling Peptides and Proteins, Laminin, Phosphoproteins, Phosphorylation, Receptors, Laminin, Transfection
J. Cell. Mol. Med.
Date: Jul. 01, 2012
PubMed ID: 21895963
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