Journal of Cell Science 116, e201-e201 (2003)
Copyright © 2003 The Company of Biologists Limited
Latent TGFß: a molecular sensor
Transforming growth factor ß (TGFß) is an important cytokine that
regulates cell growth, apoptosis and inflammation. It is secreted as part of a
latent complex containing mature TGFß, its cleaved propeptide and
latent-TGFß-binding protein (LTBP). This complex is stored in the
extracellular matrix (ECM), releasing TGF-ß in response to changes in the
ECM. On p. 217, Justin Annes
and co-workers present a novel hypothesis in which the latent TGF-ß
complex is viewed as a molecular sensor. Within this sensor, the propeptide
functions as a `detector' that senses perturbations in the ECM by interacting
with TGFß activators such as integrins and thrombospondin and responds by
releasing the `effector', mature TGFß. LTBP acts as the `localizer' of
the sensor, binding covalently to the ECM. The new model is consistent with
the phenotypes of individuals in whom latent TGFß processing or assembly
is defective and explains several puzzling aspects of TGFß biology. For
example, the fact that TGFß1, TGFß2 and TGFß3 have similar
properties and expression patterns but isoform-specific effects in vivo can
now be accounted for by differences in how their detectors respond.
Related articles in JCS:
- Making sense of latent TGFß activation
- Justin P. Annes, John S. Munger, and Daniel B Rifkin
JCS 2003 116: 217-224.
[Abstract]
[Full Text]
