DF/HCC Program Affiliation

Angiogenesis, Invasion, and Metastasis

Research Abstract

The maintenance of endothelial cells as a semi permeable monolayer lining the blood vessel lumen depends on the arrest of cell replication when endothelial cells come into contact with one another and the nature of the cell-cell contacts formed.

Protein tyrosine phosphorylation has been shown to be associated with cell density contact inhbition of growth as well as regulation of endothelial cell permeability. Tyrosine phosphorylation is coordinated regulated by protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs).

Although several PTPs have been identified, very little is known about the reversibility, and inhibition of tyrosine phosphorylation by PTKs. The major focus of my project has been to identify PTPs in endothelial cells. Using RT-PCR with degenerated primers complementary to highly conserved motifs in the catalytic PTP domains followed by low screening hybridization of endothelial cell mRNA and cDNA libraries, I identified PTPmu. PTPmu is a preferently expressed receptor-type PTPase in endothelial cells with higher levels of protein present in arterioles as compared to venules of similar caliber. Furthermore, RRTPmu protein levels is regulated by and localizes at cell-cell contacts in endothelial cells in culture and vessel endothelium in vivo.

Currently, I am studying the possible role RPTPmu may have regarding cell-cell contact and permeability using retrovirus constructs containing full length, deleted, dominant negative and soluble forms of PTPmu in transiently infected primary endothelial cells from arteriolar and venular territories.

Publications

• Bianchi C, Araujo EG, Sato K, Sellke FW.Biochemical and structural evidence for pig myocardium adherens junction disruption by cardiopulmonary bypass.Circulation 2001 Sep 18;104(12 Suppl 1):I319-24.
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• Bianchi C, Sellke FW, Del Vecchio RL, Tonks NK, Neel BG.Receptor-type protein-tyrosine phosphatase mu is expressed in specific vascular endothelial beds in vivo.Exp Cell Res 1999 Apr 10;248(1):329-38.
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• Campan M, Yoshizumi M, Seidah NG, Lee ME, Bianchi C, Haber E.Increased proteolytic processing of protein tyrosine phosphatase mu in confluent vascular endothelial cells: the role of PC5, a member of the subtilisin family.Biochemistry 1996 Mar 26;35(12):37
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