Angiogenesis: From the Molecular to Integrative Pharmacology by Michael E. Maragoudakis (auth.), Michael E. Maragoudakis

By Michael E. Maragoudakis (auth.), Michael E. Maragoudakis (eds.)

Proceedings of the fifth Biannual foreign assembly on Angiogenesis: From the Molecular to Integrative Pharmacology, held July 1-7, 1999, in Crete, Greece.
Angiogenesis, as a tremendously advanced organic method, has challenged researchers from all uncomplicated clinical disciplines, together with pharmacology, biochemistry, body structure, embryology and anatomy. the importance of this phenomenon for the research of ailment states has additionally clinicians from a few professional fields. This multidisciplinary paintings displays the expansion of information of techniques equivalent to angiogenesis established remedy, the big healing and advertisement strength of which has attracted significant learn and funding in recent times. This quantity, which goals to bridge the distance among uncomplicated and scientific technique and realizing, offers the main up to date advancements during this field.

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Cancer Res. 60: 1-41. , 1991, Neovascularization is associated with a switch to the export ofbFGF in the multistep development of fibrosarcoma, Cell 66: 1095-1104. , 1993, Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumor growth in vivo, Nature 362: 841-844. , 1993, An essential heparin-binding domain in the fibroblast growth factor receptor kinase, Science 259: 19181921. , 1993, Basic fibroblast growth factor modulates integrin expression in microvascular endothelial cells, Mol.

1. INTRODUCTION The Tie family of receptor tyrosine kinases (RTKs) consists of two These receptors are expressed members, Tie-l and Tie-2/Tek. Angiogenesis: From the Molecular to Integrative Pha17fUlc%gy Edited by MaragoudakIS, Kluwer Academic / Plenum Publishers, New York, 2000 35 36 predominantly in endothelial and haematopoietic cells 1-3 and are essential for vascular development 4,5. Tie-l and Tie-2 share similar structural features. The extracellular domains of both receptors have two immunoglobulin-like repeats separated by three EGF-homology domains and followed by three fibronectin III-like repeats.

The ligands responsible for activating Tie-I, its signalling pathways and specific cellular functions are however not known. As with some other receptor tyrosine kinases, Tie-l is subject to extracellular proteolytic cleavage generating a membrane bound receptor fragment comprising the intracellular and transmembrane domains. Here we examine the signalling potential of this Tie-l endodomain. We show that the Tie-l endodomain has poor ability to induce tyrosine phosphorylation. However, on formation the endodomain physically associates with a number of tyrosine phosphorylated signalling intermediates including the tyrosine phosphatase and adaptor protein SHP2.

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