TGF‐β control of cell proliferation

AbstractThis article focuses on recent findings that the type V TGF‐β receptor (TβR‐V), which co‐expresses with other TGF‐β receptors (TβR‐I, TβR‐II, and TβR‐III) in all normal cell types studied, is involved in growth inhibition by IGFBP‐3 and TGF‐β and that TGF‐β activity is regulated by two distinct endocytic pathways (clathrin‐ and caveolar/lipid‐raft‐mediated). TGF‐β is a potent growth inhibitor for most cell types, including epithelial and endothelial cells. The signaling by which TGF‐β controls cell proliferation is not well understood. Many lines of evidence indicate that other signaling pathways, in addition to the prominent TβR‐I/TβR‐II/Smad2/3/4 signaling cascade, are required for mediating TGF‐β‐induced growth inhibition. Recent studies revealed that TβR‐V, which is identical to LRP‐1, mediates IGF‐independent growth inhibition by IGFBP‐3 and mediates TGF‐β‐induced growth inhibition in concert with TβR‐I and TβR‐II. In addition, IRS proteins and a Ser/Thr‐specific protein phosphatase(s) are involved in the TβR‐V‐mediated growth inhibitory signaling cascade. The TβR‐V signaling cascade appears to cross‐talk with the TβR‐I/TβR‐II, insulin receptor (IR), IGF‐I receptor (IG