© 1996 American Heart Association, Inc.
Articles |
Transforming Growth Factor-ß Signal Transduction
From the Abteilung für Zell- und Molekularbiologie (T.B.), Institut für Biochemie und Biotechnologie, Technische Universität Braunschweig (Germany), and the Molecular Cardiology Unit (M.D.S.), Departments of Medicine, Cell Biology, and Molecular Physiology & Biophysics, Baylor College of Medicine, Houston, Tex.
Correspondence to Dr Michael D. Schneider, Molecular Cardiology Unit, Baylor College of Medicine, One Baylor Plaza, Room 506 C, Houston, TX 77030.
Key Words: growth factors • receptors • signal transduction
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Introduction |
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The TGF-ß superfamily of cytokines comprises an array of more than two dozen secreted peptides that have been implicated as multifunctional regulators of cell growth, differentiation, and function.1 2 Members of this family are pivotal for normal development in a variety of species, providing diffusible signals that influence pattern formation, body axes, cell fate, and other aspects of morphogenesis. In the embryonic heart, developmental functions for TGF-ß inferred from the genes' program of expression and from model systems for cardiac organogenesis include the specification of cardiogenic precursor cells in lateral mesoderm as well as epithelial-mesenchymal transitions involved in valve formation.2 In postnatal myocardium, TGF-ß controls the mixed histocompatibility genes, whose deregulation may explain the myocarditis found in mice lacking TGF-ß1. In isolated cardiac muscle cells, TGF-ß counters the suppression of myocyte contraction by interleukin-1ß, at least in part through a block to induction of nitric oxide synthase. Conversely, TGF-ß evokes a "fetal" program of myocardial gene expression, which, together with the upregulation of TGF-ß by mechanical load and other trophic signals, suggests the operation of an autocrine or paracrine loop in certain forms of cardiac hypertrophy.2
The TGF-ß superfamily consists of at least 25 different peptides,
classified into three subgroups based on sequence similarities: (1)
TGF-ßs themselves, of which three isoforms are found in mammals, (2)
activins, and (3) a complex third subfamily of proteins (BMPs, nodal,
Xenopus Vg-1, Drosophila dpp, and screw) with
prominent effects on mesoderm induction and formation of axial
structures.1 2 All known members of the superfamily
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