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Biotech / Medical : Regeneron Pharmaceuticals

REGN 693.35

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3:59 PM EST

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To: scaram(o)uche who wrote (222)	2/25/1998 10:41:00 PM
From: Miljenko Zuanic	Read Replies (1) of 3557

Rick: >>Ooooh, you know something that I don't! What's the link between RGD and Tie-2? I've missed something.<< Probably you misunderstood me. I quoted: >>Interesting similarity in aVb3/Tie-2 and Del-1/Angio-1. Curious does aVb3 have natural antagonist (Arg-Gly-Asp motive) like Tie-2? I think that researcher will now search for cross-interaction and synergetic of this two protein/receptor. Maybe exact Tie-1 rule (and its ligands) in angiogenesis is next step.<< Both aVb3 and Tie-2 are TK receptors and are activated by ligand stimulation (phosphorilation). Induction signal from EC surface to nucleus by Tie-2, and cells- cells/cells-matrix adhesion by aVb3 integrin complex. RGD motive in aVb3 ligand (Del-1) and synthetic peptides has middle Gly which is (I guess reversible for Del-1, and irreversible for synthetic peptides) phosphorilated and than bonded to integrin matrix. This does not have biochemical similarity/link with Tie-2. Tie-2 rule are in late stage of angiogenesis procedure: maturation, incorporation and maintain vessel integrity. Ang-1 signals t Tie-2 to recruit support cells. So this signal have to have some cooperation from other angiogenic factors and matrix generator. Here come integrins, and this was my connection on synergicity. Cross interaction was not the best expression. Regards the question on natural antagonist for aVb3 receptors (similar to Tie-2 and Ang-1/Ang-2), this antagonist should bind to receptor but not facilitate phosphorilation and forming integrin complex. As balance to positive ligand (very often present in nature). Interesting that (according to REGN article) Ang-2 is Tie-2 positive ligand for fibroblast cells (without proliferation) when Tie-2 are expressed, and negative ligand for EC when Tie-1 and Tie-2 are expressed. From in-vitro study REGN didn't found connection between Tie-1/Tie-2 and Ang-2(heterodimerization and inactivation), but I will not exclude this possibility for now. mz

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