PATHOLOGY & ONCOLOGY RESEARCHVol. 2 No. 1, 1996

 Article

Tyrosine Phosphorylation of a ~30 kD Protein Precedes avb3 Integrin-signaled Endothelial Cell Spreading and Motility on Matrix Proteins

Dean G TANG1, Clement A DIGLIO2, Kenneth HONN4

1Department of Radiation Oncology, Wayne State University, Detroit, USA
2Department of Pathology, Wayne State University, Detroit, USA
3Department of Chemistry, Wayne State University, Detroit, USA
4Gershenson Radiation Oncology Center, Harper Hospital, Detroit, USA

 

A microvascular endothelial cell line (CD clone 4) isolated from murine lung adheres to and spreads well on fibronectin, vitronectin, and fibrinogen, but poorly on collagen type IV and laminin. Ligating cell surface av, b3, a4, a5, or b1 integrin receptors with monospecific antibodies promoted a dramatic cell spreading and motility on vitronectin or collagen IV. Antibodies directed to other adhesion molecules, including aIIb, PECAM-1, and P-selectin were ineffective. Ligation with monoclonal anti-av or -b3, but not -a4, -a5, or -b1 antibodies, induced a rapid, and dose-dependent tyrosine phosphorylation of a ~30 kD protein, which preceded CD clone 4 endothelial cell spreading and motility and was partially inhibited by genistein and completely inhibited by BAPTA. All other antibodies tested did not induce the tyrosine phosphorylation of the 30 kD protein as well as cell spreading and motility. The present results suggest that b1 and b3 integrins employ different biochemical mechanisms in signaling endothelial cell spreading and motility and that the tyrosine phosphorylation of the 30 kD protein (and probably other proteins) may play an important role in signaling b3 integrin-mediated endothelial cell interaction with other cells (e.g., tumor cells) and extracellular matrix. Pathology & Oncology Research, Vol 2, Nr 1, 21-29, 1996

Key words: integrin; motility; spreading; tyrosin phosphorylation; extracellular matrix


Received: Jan 31, 1996; accepted: Feb 22, 1996
Correspondence: Kenneth HONN, Department of Radiation Oncology, Wayne State University, 431 Chemistry Detroit 48202, USA; Tel: (313)5771018, Fax: (313)5770798

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