Transforming growth factor-beta: a general review.

作者：David A. Lawrence · 发表于：PubMed · 年份：1996 · 被引用次数：402 · 研究领域：TGF-β signaling in diseases

Three isoforms of Transforming Growth Factor-beta (TGF-beta 1, beta 2 and beta 3) exist in mammals. They play critical roles in growth regulation and development. Each isoform is encoded by a unique gene on different chromosomes. All three of these growth factors are secreted by most cell types, generally in a latent form, requiring activation before they can exert biological activity. This activation of latent TGF-beta, which may involve plasmin, thrombospondin and possibly acidic microenvironments, appears to be a crucial regulatory step in controlling their effects. The TGF-betas possess three major activities: they inhibit proliferation of most cells, but can stimulate the growth of some mesenchymal cells; they exert immunosuppressive effects; and they enhance the formation of extracellular matrix. Two types of membrane receptors (type I and type II) possessing a serine/threonine kinase activity within their cytoplasmic domains are involved in signal transduction. Inhibition of growth by the TGF-betas stems from a blockage of the cell cycle in late G1 phase. Among the molecular participants concerned in G1-arrest are the Retinoblastoma (Rb) protein and members of the Cyclin/Cyclin-dependent kinase/Cyclin dependent kinase inhibitor families. In the intact organism the TGF-betas are involved in wound repair processes and in starting inflammatory reactions and then in their resolution. The latter effects of the TGF-betas derive in part from their chemotactic attraction of in...