Identification of a structural domain that distinguishes the actions of the type 1 and 2 isoforms of transforming growth factor beta on endothelial cells.

Abstract:

:A chimeric transforming growth factor beta (TGF-beta) molecule has been synthesized to map the amino acids responsible for the substantially greater activity of TGF-beta 1 than TGF-beta 2 on growth and migration of endothelial cells. This chimera consists of a dimer of a monomeric unit composed of amino acids 1-39 of TGF-beta 2, 40-82 of TGF-beta 1, and 83-112 of TGF-beta 2. Structural identity of the purified recombinant protein has been confirmed by immunoblotting and NH2-terminal sequencing. The biological potency of the TGF-beta 2-1-2 chimera was equal to that of TGF-beta 1 in inhibition of growth of both fetal bovine heart endothelial cells and rat epididymal fat pad microvascular endothelial cells. Similarly, the TGF-beta 2-1-2 chimera was nearly equivalent to TGF-beta 1 and at least 10-fold more active than TGF-beta 2 in inhibiting migration of bovine aortic endothelial cells. These results identify the sequence between amino acids 40-82 as an important region within TGF-beta that functions to specify a TGF-beta 1- or TGF-beta 2-like activity.

authors

Qian SW,Burmester JK,Merwin JR,Madri JA,Sporn MB,Roberts AB

doi

10.1073/pnas.89.14.6290

keywords:

subject

Has Abstract

pub_date

1992-07-15 00:00:00

pages

6290-4

issue

14

eissn

0027-8424

issn

1091-6490

journal_volume

89

pub_type

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