INACTIVATION OF THE TYPE-II RECEPTOR REVEALS 2 RECEPTOR PATHWAYS FOR THE DIVERSE TGF-BETA ACTIVITIES

Transforming growth factor-beta (TGF-beta) is a multifunctional protei n that regulates cell proliferation and differentiation and extracellu lar matrix production. Although two receptor types, the type I and typ e II receptors, have been implicated in TGF-beta-induced signaling, it is unclear how the many activities of TGF-beta are mediated through t hese receptors. With the use of cells overexpressing truncated type II receptors as dominant negative mutants to selectively block type II r eceptor signaling, the existence of two receptor pathways was shown. T he type II receptors, possibly in conjunction with type I receptors, m ediate the induction of growth inhibition and hypophosphorylation of t he retinoblastoma gene product pRB. The type I receptors are responsib le for effects on extracellular matrix, such as the induction of fibro nectin and plasminogen activator inhibitor I, and for increased JunB e xpression. Selective inactivation of the type II receptors alters the TGF-beta response in a similar manner to the functional inactivation o f pRB, suggesting a role for pRB in the type II, but not the type I, r eceptor pathway.