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Fig. 2. The latent TGFß sensor model. The figure depicts the sequential events
in the bioavailability of TGFß, from synthesis to signaling consequences,
according to consideration of the TGFß LLC as a sensor. Sensor assembly
(1) occurs cotranslationally when the localizer (LTBP; L) is covalently linked
to pro-TGFß (D-E). As shown, the next step (step 2) is the proteolytic
cleavage of the bonds between the detector (LAP; D) and the effector
(TGFß; E). This step turns the sensor `on' or, in other words, makes the
sensor competent (note that the timing of this step is variable and may occur
after secretion). Once secreted, the sensor is stored in the ECM (step 3).
Subsequently, the complex may be solubilized from the matrix (step 4) by
cleavage of LTBP in the hinge region. This soluble form of TGFß is still
latent and may be activated (step 5). Under other conditions, activation of
the matrix-bound sensor occurs (step 5'). Binding of liberated TGFß
(E) to its receptors (step 6) with subsequent signal transduction has multiple
results (green arrows; A), including induction of TGFß expression (B),
enhanced expression of transcripts encoding TGFß activators (C), and
increased synthesis of ECM components (D).
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