Measuring Interactions Between ECM and TGFB-Like Proteins - Methods in Molecular Biology: Extracellular Matrix Protocols - page 221

Fig. 1. Proposed model showing the role of LTBP1 in regulating TGF β activity and

homodimer, which
is cleaved from, but remains non-covalently associated with the 75 KDa propeptide.
LTBP1 (190 KDa) is complexed with latent TGF

availability. (1) Latent TGF β consists of the mature 25 KDa TGF β

inside the cell and facilitates its
secretion. (2) LTBP1 acts as a carrier to transport latent TGF

β

β to the matrix for storage.

(3) LTBP1 facilitates release of latent TGF from matrix by undergoing proteolysis,

releasing an approx 130 KDa cleaved fragment of LTBP1 complexed to latent TGF

β

β.
(4) This cleaved fragment of LTBP1, which is protase-resistant, protects the latent
complex from activation until it reaches an appropriate target cell. LTBP1 may then
play a further role in activation of latent TGF β .

fibrillins and three of the family members are known to bind transforming
growth factor betas (TGF s) and influence their availability (2-4 , 6) . LTBP1 is

complexed with latent TGF

β

prior to secretion and tightly regulates the activ-
ity of this growth factor at multiple levels (summarized in Fig. 1 ). LTBP1
facilitates secretion of latent TGF

β

from the cell (8) , and then provides a vehicle
for storage of the growth factor in the matrix (9-11) . Matrix-bound LTBP1 is
highly insoluble because of the fact that it is crosslinked via the action of
transglutaminase (12) . However, LTBP1 has a proteinase sensitive “hinge”

β