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Latency and activation in the control of TGF-β

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Abstract

The biological activity of the transforming growth factor-β's (TGF-β)3 is tightly controlled by their persistance in the extracellular compartment as latent complexes. Each of the three mammalian isoform genes encodes a product that is cleaved intracellularly to form two polypeptides, each of which dimerizes. Mature TGF-β, a 24 kD homodimer, is noncovalently associated with the 80 kD latency-associated peptide (LAP). LAP is a fundamental component of TGF-β that is required for its efficient secretion, prevents it from binding to ubiquitous cell surface receptors, and maintains its availability in a large extracellular reservoir that is readily accessed by activation. This latent TGF-β complex (LTGF-β) is secreted by all cells and is abundant both in circulating forms and bound to the extracellular matrix. Activation describes the collective events leading to the release of TGF-β. Despite the importance of TGF-β regulation of growth and differentiation in physiological and malignant tissue processes, remarkably little is known about the mechanisms of activationin situ. Recent studies of irradiated mammary gland reveal certain features of TGF-β1 activation that may shed light on its regulation and potential roles in the normal and neoplastic mammary gland.

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Abbreviations

TGF-β:

Transforming growth factor β1

LTGF-β:

latent transforming growth factor β1

LAP:

latency associated peptide

ROS:

reactive oxygen species

tPA:

tissue-type plasminogen activator

PAI:

plasminogen activator inhibitor-1

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  1. Life Sciences Division, E. O. Lawrence Berkeley National Laboratory, University of California, Building 74-166, 1 Cyclotron Road, 94720, Berkeley, California

    Mary Helen Barcellos-Hoff

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Barcellos-Hoff, M.H. Latency and activation in the control of TGF-β. J Mammary Gland Biol Neoplasia 1, 353–363 (1996). https://doi.org/10.1007/BF02017391

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