Regulation of cell–cell interactions by phosphatidic acid phosphatase 2b/VCIP

AUTOR(ES)

Humtsoe, Joseph O.

FONTE

Oxford University Press

RESUMO

We identified vascular endothelial growth factor and type I collagen inducible protein (VCIP), also known as phosphatidic acid phosphatase 2b (PAP2b), in a functional assay of angiogenesis. VCIP/PAP2b exhibits an Arg–Gly–Asp (RGD) cell adhesion sequence. Immunoprecipitation and fluorescence-activated cell sorting analyses demonstrated that VCIP-RGD is exposed to the outside of the cell surface. Retroviral transduction of VCIP induced cell aggregation/cell– cell interactions, modestly increased p120 catenin expression and promoted activation of the Fak, Akt and GSK3β protein kinases. Furthermore, expression of recombinant VCIP promoted adhesion, spreading and tyrosine phosphorylation of Fak, Shc, Cas and paxillin in endothelial cells. GST–VCIP-RGD, but not GST–VCIP-RGE, specifically interacted with a subset of integrins, and these interactions were effectively blocked by anti-αvβ3 and anti-α5β1 integrin antibodies, and by PAP2b/VCIP-derived peptides. Interestingly, PAP2b/VCIP is expressed in close proximity to vascular endothelial growth factor, von Willebrand factor and αvβ3 integrin in tumor vasculatures. These findings demonstrate an unexpected function of PAP2b/VCIP, and represent an important step towards understanding the molecular mechanisms by which PAP2b/VCIP-induced cell–cell interactions regulate specific intracellular signaling pathways.

Documentos Relacionados

• Regulation of A-currents by cell-cell interactions and neurotrophic factors in developing chick parasympathetic neurones.
• Inhibition of cell-cell interactions in Myxococcus xanthus by congo red.
• Cell-cell interactions in synovitis: Interactions between T cells and B cells in rheumatoid arthritis
• Escherichia coli K-12 cell-cell interactions seen by time-lapse video.
• Cell-cell interactions in synovitis: Interactions between T lymphocytes and synovial cells