Biology Reference
In-Depth Information
19
Measuring Interactions
Between ECM and TGF
β
-Like Proteins
Sarah L. Dallas
1. Introduction
Recent advances in developmental biology have highlighted the importance
of the synergistic relationships between structural components of the extracel-
lular matrix (ECM) and growth factors that play fundamental roles in tissue
morphogenesis and repair. Increasing evidence suggests that the binding of
growth factors to the ECM is a major mechanism for regulation of growth
factor activity (for review see ref. (1) . Association of growth factors with the
ECM allows storage of large quantities of growth factors in a readily mobi-
lized form, which could allow extracellular signaling to proceed rapidly in the
absence of new protein synthesis. This may be particularly important in situa-
tions such as tissue repair following injury. Storage of growth factors in the
ECM may also facilitate communication between cells that are widely sepa-
rated in time, by allowing transmission of signals from one cell to a different
cell that comes in contact with the same matrix later. Another intriguing possi-
bility is that matrix-bound growth factors could act as a “memory,” which pro-
vides information about the history of cellular activity of the tissue. Finally, it
is possible that matrix-bound growth factors may actually signal differently
than their soluble counterparts, for example by escaping internalization after
binding to receptors, thus producing an extended signal. Thus matrix-bound
growth factors may provide an important new dimension to cell-cell commu-
nication by greatly increasing the diversity of action of growth factors.
An example of a matrix protein that is important in growth factor regulation
is the latent transforming growth factor beta binding protein-1 (LTBP1).
LTBP1 is a member of an emerging superfamily of ECM proteins, which
includes LTBPs 1, 2, 3, and 4 (2-7) . These proteins have homology to the
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