Regulation of cell-cell interactions by phosphatidic acid phosphatase 2b/VCIP.
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 GSK3beta 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-alpha(v)beta(3) and anti-alpha(5)beta(1) 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 alpha(v)beta(3) 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.
Humtsoe
Joseph O
JO
Center for Extracellular Matrix Biology, Institute of Biosciences and Technology, Texas Medical Center, 2121 W Holcombe Blvd, Houston, TX 77030, USA.
Feng
Shu
S
Thakker
Geeta D
GD
Yang
Jun
J
Hong
Jun
J
Wary
Kishore K
KK
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002448:Cell Adhesion / Q000502:physiology*; D002460:Cell Line; D017931:DNA Primers; D006801:Humans; D039081:Integrin alpha5beta1 / Q000378:metabolism; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D008969:Molecular Sequence Data; D010711:Phosphatidate Phosphatase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000502:physiology; D014161:Transduction, Genetic
D017931:DNA Primers; D039081:Integrin alpha5beta1; D039302:Integrin alphaVbeta3; D011994:Recombinant Proteins; C406242:phosphatidic acid phosphatase type 2; D010711:Phosphatidate Phosphatase