Enhancement of endothelial cell migration and in vitro tube formation by TAP20, a novel beta 5 integrin-modulating, PKC theta-dependent protein.
Migration, proliferation, and tube formation of endothelial cells are regulated by a protein kinase C isoenzyme PKCtheta. A full-length cDNA encoding a novel 20-kD protein, whose expression was PKCtheta-dependent, was identified in endothelial cells, cloned, characterized, and designated as theta-associated protein (TAP) 20. Overexpression of TAP20 decreased cell adhesion and enhanced migration on vitronectin and tube formation in three-dimensional culture. An antiintegrin alphavbeta5 antibody prevented these TAP20 effects. Overexpression of TAP20 also decreased focal adhesion formation in alphavbeta3-deficient cells. The interaction between TAP20 and beta5 integrin cytoplasmic domain was demonstrated by protein coprecipitation and immunoblotting. Thus, the discovery of TAP20, which interacts with integrin beta5 and modulates cell adhesion, migration, and tube formation, further defines a possible pathway to angiogenesis dependent on PKCtheta.
Tang
S
S
Cardiovascular Division, Department of Medicine, Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461, USA. tang@aecom.yu.edu
Gao
Y
Y
Ware
J A
JA
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002448:Cell Adhesion / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000737:chemistry; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D006801:Humans; D039641:Integrin beta Chains; D016023:Integrins / Q000378:metabolism / Q000502:physiology*; D007527:Isoenzymes / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D018919:Neovascularization, Physiologic / Q000502:physiology; D009687:Nuclear Proteins; D011493:Protein Kinase C / Q000502:physiology*; D000074121:Protein Kinase C-theta; D011506:Proteins / Q000737:chemistry; D051381:Rats; D019030:Receptors, Vitronectin / Q000378:metabolism; D014407:Tumor Cells, Cultured; D016335:Zinc Fingers
C403295:ITGB3BP protein, human; D039641:Integrin beta Chains; D016023:Integrins; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D009687:Nuclear Proteins; D011506:Proteins; D019030:Receptors, Vitronectin; C402245:TAP20 protein, rat; C084344:integrin beta5; C076233:PRKCQ protein, human; C489591:Prkcq protein, rat; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta