The traditional high-affinity receptor for TGF-beta 1 is a heteromeric complex consisting of transmembrane
serine/threonine kinases. Two types are involved; a constitutively phosphorylated, ligand-binding
80 kDa glycoprotein termed T beta RII and a signal-transducing, non-ligand-binding 55 kDa glycoprotein
termed T beta RI/ALK-5 (19-22). It is suggested that TGF-beta 1first binds T beta RII, which then initiates a crossphosphorylation of T beta RI, culminating in signal transduction. There is also a third TGF-beta receptor termed
T beta RIII, which can be either the 250 kDa proteoglycan named betaglycan, or the 180 kDa glycoprotein
termed endoglin/CD105 (23, 24). It has been proposed that T beta RIII captures TGF-beta and "passes" it to
T beta RII (20). This is perhaps true for betaglycan but not endoglin. Endoglin does not bind TGF-beta by itself;
only within the context of T beta RII ligand binding. Evidence suggests that rather than "passing" on ligand,
endoglin may actually enter the receptor complex and modulate TGF-beta downstream signaling (25, 26).
Finally, and although ALK-5 has traditionally been assumed to be the only type I signaling receptor for
TGF-beta 1, it is also possible that ALK-1 may serve as a condition-dependent, type I TGF-beta receptor (27).
TGF-beta 1 has a wide range of activities. During an immune response, TGF-beta 1 impacts antibody
production by preferentially induceing IgA production in both mouse and human (28). It also regulates
dendritic cell chemotaxis by altering the expression of chemokine receptors (29). Finally, it can
downmodulate an inflammatory response by dampening macrophage activity and proinflammatory
secretion (30). During wound healing, TGF-beta 1 is released from activated platelets. This local source of
TGF-beta 1 has marked stimulatory effects on fibroblasts, where it induces matrix synthesis; on monocytes,
where it induces proinflammatory mediator and growth factor secretion; and on keratinocytes, where
it may promote keratinocyte proliferation by downmodulating its own signaling pathway (31). Finally,
during development, TGF-beta 1 may play a role in endochondral ossification, and its absence results in
severely defective yolk sac vasculogenesis and hematopoiesis (32, 33).
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